{"format":{"id":"antibody","name":"Naked antibodies","blurb":"A target and an antibody format: whether the Fc is engineered to recruit killer cells, silenced to avoid them, fused to a trap, or copied as a biosimilar.","route":"/modalities/antibody/","engine":"/pipeline/engine/antibody/"},"counts":{"drugs":149,"approved":61,"phase3":44,"trials":640,"companies":117,"papers":203,"ideas":111,"eras":11},"how":{"paragraphs":["Lab-made immune proteins that lock onto one target, either blocking it or flagging the cell for destruction.","A humanised or fully human IgG binds a surface or soluble antigen; Fc engineering tunes effector function and half-life."],"from":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"technologies":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/","status":"standard-of-care","tldr":"Lab-made immune proteins that lock onto one target, either blocking it or flagging the cell for destruction."},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/","status":"standard-of-care","tldr":"Immune checkpoint inhibitors are antibodies against CTLA-4, PD-1 or PD-L1 that release the brakes on T cells so they attack the cancer. They are approved in more than 20 tumour types and produce lasting, sometimes curative responses that chemotherapy rarely does, but most patients do not respond and autoimmune side effects are the cost."},{"id":"cd47-blockade","kind":"technology","name":"CD47 and SIRP-alpha blockade","route":"/technologies/cd47-blockade/","status":"phase-2","tldr":"Drugs that remove the 'don't eat me' signal cancer cells show to macrophages, so the immune system's scavenger cells can engulf them; the lead programme was halted for safety."},{"id":"cd40-agonists","kind":"technology","name":"CD40 agonist antibodies","route":"/technologies/cd40-agonists/","status":"phase-2","tldr":"Antibodies that switch on CD40 on dendritic cells and macrophages to kick-start an immune response against tumours that checkpoint drugs alone cannot reach."},{"id":"monoclonal-antibody-manufacturing","kind":"technology","name":"Antibody manufacturing (CHO bioprocessing)","route":"/technologies/monoclonal-antibody-manufacturing/","status":"standard-of-care","tldr":"Antibody manufacturing means growing antibody drugs like pembrolizumab or trastuzumab in vats of engineered hamster cells, then purifying them. 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More mutations mean more targets for the immune system.","category":"Biomarkers"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/","tldr":"Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise. It is found in a fraction of colorectal and endometrial cancers and was the basis of the first tumour-agnostic approval, pembrolizumab in 2017.","category":"Biomarkers"},{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/","tldr":"Immune-related adverse events (irAEs) are the autoimmune side effects of checkpoint inhibitors: colitis, thyroid problems, rash, hepatitis, pneumonitis.","category":"Side effects"}],"engine":{"route":"/pipeline/engine/antibody/","axes":["Target","Antibody format"],"rows":48,"cols":6,"counts":{"approved":34,"development":38,"stopped":3,"unclear":0,"untried":243},"placed":116,"total":149,"pct":78},"approved":[{"drug":{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},"brand":"Rituxan / MabThera (and biosimilars)","status":"approved","modality":"Monoclonal antibody (anti-CD20, chimeric)","cancers":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"nodular-lymphocyte-predominant-hodgkin-lymphoma","kind":"cancer","name":"Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma)","route":"/cancers/nodular-lymphocyte-predominant-hodgkin-lymphoma/"}],"indications":["Relapsed follicular lymphoma; 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later ovarian, cervical, RCC, glioblastoma, HCC","Refractory mCRC with trifluridine/tipiracil (SUNLIGHT)","Platinum-resistant ovarian cancer with chemotherapy; recurrent/metastatic cervical cancer with chemotherapy","First-line stage III-IV ovarian cancer after surgery","First-line maintenance with olaparib in HRD-positive ovarian cancer"],"years":[2004,2006,2014,2018,2020,2023],"firstYear":2004,"regions":["US"],"target":{"key":"target","id":"vegf","name":"VEGF / VEGFR","href":"/targets/vegf/"},"companies":[{"id":"anbogen-therapeutics","kind":"company","name":"Anbogen Therapeutics","route":"/companies/anbogen-therapeutics/"},{"id":"bio-thera-solutions","kind":"company","name":"Bio-Thera Solutions","route":"/companies/bio-thera-solutions/"},{"id":"biocon","kind":"company","name":"Biocon","route":"/companies/biocon/"},{"id":"biocon-biologics","kind":"company","name":"Biocon Biologics","route":"/companies/biocon-biologics/"},{"id":"gi-innovation","kind":"company","name":"GI Innovation","route":"/companies/gi-innovation/"},{"id":"hetero","kind":"company","name":"Hetero Drugs","route":"/companies/hetero/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"},{"id":"samsung-bioepis","kind":"company","name":"Samsung Bioepis","route":"/companies/samsung-bioepis/"}]},{"drug":{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},"brand":"Erbitux","status":"approved","modality":"Monoclonal antibody (anti-EGFR)","cancers":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"recurrent-metastatic-hnscc","kind":"cancer","name":"Recurrent or metastatic head and neck squamous cell carcinoma","route":"/cancers/recurrent-metastatic-hnscc/"},{"id":"hpv-negative-head-and-neck-cancer","kind":"cancer","name":"HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)","route":"/cancers/hpv-negative-head-and-neck-cancer/"}],"indications":["EGFR-expressing metastatic colorectal cancer (later restricted to RAS wild-type)","Head and neck squamous cell carcinoma with radiation","BRAF V600E mCRC with encorafenib","KRAS G12C mCRC with adagrasib"],"years":[2004,2006,2020,2024],"firstYear":2004,"regions":["US"],"target":{"key":"target","id":"egfr","name":"EGFR","href":"/targets/egfr/"},"companies":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. 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(MSD)","route":"/companies/merck/"},{"id":"merck-kgaa","kind":"company","name":"Merck KGaA (EMD Serono)","route":"/companies/merck-kgaa/"}]},{"drug":{"id":"human-normal-immunoglobulin","kind":"drug","name":"Human normal immunoglobulin (IVIg)","route":"/drugs/human-normal-immunoglobulin/"},"brand":"Privigen / Kiovig","status":"approved","modality":"Pooled human polyclonal IgG antibody preparation (intravenous immunoglobulin)","cancers":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"}],"indications":["Replacement therapy in hypogammaglobulinaemia with recurrent bacterial infections in CLL (after failed antibiotic prophylaxis) and plateau-phase multiple myeloma (after failed pneumococcal immunisation); primary immunodeficiency"],"years":[2006],"firstYear":2006,"regions":["EU"],"companies":[{"id":"csl","kind":"company","name":"CSL 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alemtuzumab (conditional; authorisation since withdrawn)"],"years":[2009,2010,2014],"firstYear":2009,"regions":["US","EU"],"target":{"key":"target","id":"cd20","name":"CD20","href":"/targets/cd20/"},"companies":[{"id":"genmab","kind":"company","name":"Genmab","route":"/companies/genmab/"},{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}]},{"drug":{"id":"denosumab","kind":"drug","name":"Denosumab","route":"/drugs/denosumab/"},"brand":"Xgeva / Prolia","status":"approved","modality":"Monoclonal antibody (anti-RANKL, fully human IgG2)","cancers":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung 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FOLFIRI"],"years":[2012,2013],"firstYear":2012,"regions":["US","EU"],"target":{"key":"target","id":"vegf","name":"VEGF / VEGFR","href":"/targets/vegf/"},"companies":[{"id":"regeneron","kind":"company","name":"Regeneron","route":"/companies/regeneron/"},{"id":"sanofi","kind":"company","name":"Sanofi","route":"/companies/sanofi/"}]},{"drug":{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"},"brand":"Gazyva","status":"approved","modality":"Monoclonal antibody (anti-CD20, glycoengineered type II)","cancers":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"}],"indications":["Previously untreated CLL with chlorambucil (CLL11)","Previously untreated CLL with venetoclax, fixed duration (CLL14); with acalabrutinib (ELEVATE-TN)"],"years":[2013,2019],"firstYear":2013,"regions":["US"],"target":{"key":"target","id":"cd20","name":"CD20","href":"/targets/cd20/"},"companies":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}]},{"drug":{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},"brand":"Opdivo / Opdivo Qvantig (SC)","status":"approved","modality":"Monoclonal antibody (anti-PD-1)","cancers":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"colorectal","kind":"cancer","name":"Colorectal 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The routes are loss of antigen presentation, no T cells in the tumour, and a suppressive microenvironment.","route":"/resistance/#pd1-blockade","exemplars":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}],"mechanisms":[{"name":"Loss of antigen presentation (B2M, HLA, JAK1/2)","category":"immune-evasion","categoryLabel":"Immune evasion","how":"Mutations in B2M or HLA class I stop tumour cells displaying antigen; JAK1/2 loss removes interferon responsiveness (and PD-L1 induction).","frequency":"Acquired resistance in melanoma: ~25% JAK/B2M","route":"/resistance/#pd1-blockade-loss-of-antigen-presentation-b2m-hla-jak1-2"},{"name":"Immune-desert / excluded tumours","category":"immune-evasion","categoryLabel":"Immune evasion","how":"No pre-existing T-cell infiltrate (cold tumour) 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and death have followed high doses, and the pump that keeps it out of the brain is the key factor.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-rockwell-ivermectin-benzimidazole-prescribing-jama-netw-open-2026","kind":"paper","name":"Ivermectin-benzimidazole prescribing following celebrity endorsement","route":"/key-papers/paper-rockwell-ivermectin-benzimidazole-prescribing-jama-netw-open-2026/","year":2026,"journal":"JAMA Network Open","paperType":"observational","tldr":"After a January 2025 podcast promoted ivermectin with a dog dewormer as a cancer cure, US prescriptions of the combination doubled overall and rose 2.6-fold among people with cancer, most steeply in the South.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-saperstein-ivermectin-neurotoxicity-breast-cancer-2026","kind":"paper","name":"Life-threatening neurotoxicity following off-label ivermectin use in metastatic breast cancer: a case report","route":"/key-papers/paper-saperstein-ivermectin-neurotoxicity-breast-cancer-2026/","year":2026,"journal":"Postgraduate Medicine","paperType":"observational","tldr":"A 73-year-old woman with metastatic breast cancer took high doses of ivermectin after reading about it online, had seizures and stopped breathing adequately, and spent two days on a ventilator before recovering fully.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-cheng-melanoma-ctdna-antiparasitic-front-oncol-2026","kind":"paper","name":"Metastatic melanoma with initial ctDNA decline and radiographic response during self-directed antiparasitic use: treatment effect or spontaneous regression?","route":"/key-papers/paper-cheng-melanoma-ctdna-antiparasitic-front-oncol-2026/","year":2026,"journal":"Frontiers in Oncology","paperType":"observational","tldr":"A man with metastatic melanoma who refused standard treatment and took ivermectin and fenbendazole saw his tumour markers and scans improve for a while, then worsen; his oncologists judged spontaneous immune regression at least as likely as any drug effect.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-nci9673-part-b-nivolumab-ipilimumab-anal-cancer-morris-jco-2026","kind":"paper","name":"NCI9673 part B: randomised phase 2 study of nivolumab with or without ipilimumab in refractory metastatic anal cancer","route":"/key-papers/paper-nci9673-part-b-nivolumab-ipilimumab-anal-cancer-morris-jco-2026/","year":2026,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding ipilimumab to nivolumab for metastatic anal cancer after chemotherapy did not improve response, progression-free survival or overall survival and doubled severe side 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verified.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-amplify-acalabrutinib-venetoclax-nejm-2025","kind":"paper","name":"AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients","route":"/key-papers/paper-amplify-acalabrutinib-venetoclax-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In AMPLIFY, an all-oral, 14-month course of acalabrutinib plus venetoclax beat FCR or BR chemo-immunotherapy in fit CLL patients, offering a time-limited alternative to indefinite pills.","via":[{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"}]},{"id":"paper-aquila-daratumumab-smouldering-nejm-2025","kind":"paper","name":"AQUILA: daratumumab versus active monitoring in high-risk smouldering multiple 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subtypes.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-c-post-adjuvant-cemiplimab-nejm-2025","kind":"paper","name":"C-POST: adjuvant cemiplimab versus placebo in high-risk cutaneous squamous cell carcinoma","route":"/key-papers/paper-c-post-adjuvant-cemiplimab-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A year of cemiplimab after surgery and radiotherapy for high-risk cutaneous squamous cell carcinoma cut the risk of recurrence or death by more than two thirds, the first adjuvant therapy to work in this skin cancer.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-cepheus-dara-vrd-natmed-2025","kind":"paper","name":"CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint","route":"/key-papers/paper-cepheus-dara-vrd-natmed-2025/","year":2025,"journal":"Nature Medicine","paperType":"rct","tldr":"In patients who were transplant-ineligible or deferred transplant, the daratumumab quadruplet raised deep-remission rates from about 39% to 61% and cut progression risk by 43%.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-checkmate-067-ten-year-nejm-2025","kind":"paper","name":"CheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade later","route":"/key-papers/paper-checkmate-067-ten-year-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Ten-year follow-up of the trial that established combination checkpoint blockade shows median survival over six years with nivolumab plus ipilimumab and a plateau in the survival curve consistent with cure.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-checkmate-067-10-year-nejm-2025","kind":"paper","name":"CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma","route":"/key-papers/paper-checkmate-067-10-year-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Ten years after starting treatment, about half of patients with advanced melanoma treated with nivolumab plus ipilimumab were still alive, most without any further treatment, showing that immunotherapy can cure a disease that once killed most patients within a year.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-checkmate-8hw-lancet-2025","kind":"paper","name":"CheckMate 8HW: nivolumab plus ipilimumab versus nivolumab alone in MSI-high metastatic colorectal cancer","route":"/key-papers/paper-checkmate-8hw-lancet-2025/","year":2025,"journal":"The Lancet","paperType":"rct","tldr":"Dual immunotherapy with nivolumab and ipilimumab delayed progression more than nivolumab alone across all lines of treatment in microsatellite-unstable colorectal cancer, with about seven in ten patients progression-free at three years.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-topaz-1-three-year-survival-j-hepatol-2025","kind":"paper","name":"Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study","route":"/key-papers/paper-topaz-1-three-year-survival-j-hepatol-2025/","year":2025,"journal":"Journal of Hepatology","paperType":"rct","tldr":"Three and a half years on, adding durvalumab to chemotherapy for advanced bile duct and gallbladder cancer still showed a survival edge, and about one in seven patients were alive at three years compared with one in fourteen on chemotherapy alone.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-emerald-1-lancet-2025","kind":"paper","name":"EMERALD-1: durvalumab with or without bevacizumab added to transarterial chemoembolisation for embolisation-eligible hepatocellular carcinoma","route":"/key-papers/paper-emerald-1-lancet-2025/","year":2025,"journal":"The Lancet","paperType":"rct","tldr":"Adding durvalumab and bevacizumab to chemoembolisation lengthened the time to progression by about seven months in liver cancer suitable for embolisation, the first systemic combination to improve on chemoembolisation alone.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-harmoni-2-lancet-2025","kind":"paper","name":"HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer","route":"/key-papers/paper-harmoni-2-lancet-2025/","year":2025,"journal":"The Lancet","paperType":"rct","tldr":"In the first randomised trial to beat pembrolizumab directly, a single antibody that blocks both PD-1 and VEGF nearly doubled the time to progression in PD-L1-positive lung cancer, though survival data were still immature.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-imvigor011-nejm-2025","kind":"paper","name":"IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery","route":"/key-papers/paper-imvigor011-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Patients whose blood turned positive for tumour DNA after cystectomy lived longer with atezolizumab than placebo; patients who stayed ctDNA-negative did well without any treatment. It is the first ctDNA-guided adjuvant trial to improve survival.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-mujumdar-ivermectin-gynaecological-cancer-2025","kind":"paper","name":"Ivermectin and gynecologic cancer: what's the data?","route":"/key-papers/paper-mujumdar-ivermectin-gynaecological-cancer-2025/","year":2025,"journal":"Gynecologic Oncology Reports","paperType":"review","tldr":"Gynaecological oncologists reviewed the evidence for ivermectin in womb, ovarian and cervical cancers, found only cell-line data, and strongly caution against using it.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-patel-ivermectin-cancer-curr-oncol-rep-2025","kind":"paper","name":"Ivermectin in cancer treatment: should healthcare providers caution or explore its therapeutic potential?","route":"/key-papers/paper-patel-ivermectin-cancer-curr-oncol-rep-2025/","year":2025,"journal":"Current Oncology Reports","paperType":"review","tldr":"A 2025 review that weighs the laboratory promise against the absence of human trials and concludes that clinicians should counter misinformation while supporting proper trials.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-straughn-ivermectin-hope-versus-hype-2025","kind":"paper","name":"Ivermectin treatment for gynecologic cancers: hope versus hype","route":"/key-papers/paper-straughn-ivermectin-hope-versus-hype-2025/","year":2025,"journal":"Gynecologic Oncology Reports","paperType":"review","tldr":"An editorial accompanying the gynaecological review: repurposing is legitimate and early trials deserve support, but no major oncology organisation endorses ivermectin for cancer and patients should not forgo proven treatment for it.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-keynote-689-nejm-2025","kind":"paper","name":"KEYNOTE-689: neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck cancer","route":"/key-papers/paper-keynote-689-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Giving pembrolizumab before surgery and continuing it afterwards alongside radiotherapy reduced recurrences in resectable locally advanced head and neck cancer, the first improvement in surgical treatment of the disease in two decades.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-leap-012-lancet-2025","kind":"paper","name":"LEAP-012: transarterial chemoembolisation with lenvatinib plus pembrolizumab versus placebo for unresectable non-metastatic hepatocellular carcinoma","route":"/key-papers/paper-leap-012-lancet-2025/","year":2025,"journal":"The Lancet","paperType":"rct","tldr":"Adding lenvatinib and pembrolizumab to chemoembolisation delayed progression in intermediate-stage liver cancer, the second trial to show that systemic therapy improves on embolisation alone, at the cost of more side effects.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-matterhorn-nejm-2025","kind":"paper","name":"MATTERHORN: perioperative durvalumab with FLOT chemotherapy for resectable gastric and gastro-oesophageal junction cancer","route":"/key-papers/paper-matterhorn-nejm-2025/","year":2025,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding durvalumab to perioperative FLOT chemotherapy for operable stomach cancer reduced recurrences and doubled the rate of complete pathological response, the first immunotherapy to improve outcomes in curable gastric cancer.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-pod1um-303-retifanlimab-anal-cancer-rao-lancet-2025","kind":"paper","name":"POD1UM-303/InterAACT-2: retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic anal squamous cell carcinoma","route":"/key-papers/paper-pod1um-303-retifanlimab-anal-cancer-rao-lancet-2025/","year":2025,"journal":"The Lancet","paperType":"rct","tldr":"Adding the PD-1 antibody retifanlimab to first-line carboplatin and paclitaxel for advanced anal cancer lengthened the time before the cancer progressed from 7.4 to 9.3 months and cut the risk of progression by 37 percent, with manageable extra toxicity.","via":[{"id":"retifanlimab","kind":"drug","name":"Retifanlimab","route":"/drugs/retifanlimab/"}]},{"id":"paper-zhu-population-specific-immunogenomics-gallbladder-cancer-mod-pathol-2025","kind":"paper","name":"Population-Specific Immunogenomic Alterations in Gallbladder Cancer and Prognostic Significance","route":"/key-papers/paper-zhu-population-specific-immunogenomics-gallbladder-cancer-mod-pathol-2025/","year":2025,"journal":"Modern Pathology","paperType":"translational","tldr":"Gallbladder tumours from the United States and Chile carried the same set of mutated genes but very different immune cell make-up, which may bear on why immunotherapy helps only modestly and on how trials should be designed across regions.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-st-gallen-2025-consensus-ann-oncol-2025","kind":"paper","name":"Tailoring treatment to cancer risk and patient preference: the 2025 St Gallen International Breast Cancer Consensus Statement on individualizing therapy for patients with early breast cancer","route":"/key-papers/paper-st-gallen-2025-consensus-ann-oncol-2025/","year":2025,"journal":"Annals of Oncology","paperType":"guideline","tldr":"The 2025 international consensus on early breast cancer, which recommends platinum chemotherapy and immunotherapy for triple-negative disease, updated genetic testing guidance and shorter radiotherapy schedules.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-gilene-ivermectin-toxicity-paediatric-oncology-2025","kind":"paper","name":"The threat of medical misinformation: a case of ivermectin toxicity in a pediatric oncology patient","route":"/key-papers/paper-gilene-ivermectin-toxicity-paediatric-oncology-2025/","year":2025,"journal":"Pediatric Blood & Cancer","paperType":"observational","tldr":"A letter describing severe ivermectin poisoning in a young patient with bone cancer who was also taking regorafenib, a cancer drug that shares the enzyme ivermectin is cleared by.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-adriatic-nejm-2024","kind":"paper","name":"ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancer","route":"/key-papers/paper-adriatic-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"For small-cell lung cancer confined to the chest, adding two years of durvalumab after chemoradiotherapy extended median survival from under three years to over four and a half, the first advance in this setting in decades.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-continuum-sintilimab-nasopharyngeal-liu-lancet-2024","kind":"paper","name":"CONTINUUM: induction-concurrent chemoradiotherapy with or without sintilimab in locoregionally advanced nasopharyngeal carcinoma","route":"/key-papers/paper-continuum-sintilimab-nasopharyngeal-liu-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"Adding the PD-1 antibody sintilimab to chemotherapy and radiotherapy for advanced, non-metastatic nasopharyngeal cancer raised three-year event-free survival from 76 to 86 percent, with more but manageable side effects.","via":[{"id":"sintilimab","kind":"drug","name":"Sintilimab","route":"/drugs/sintilimab/"}]},{"id":"paper-destiny-pantumor02-jco-2024","kind":"paper","name":"DESTINY-PanTumor02: trastuzumab deruxtecan in HER2-expressing solid tumours","route":"/key-papers/paper-destiny-pantumor02-jco-2024/","year":2024,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Across seven tumour types including endometrial, cervical and ovarian cancers, trastuzumab deruxtecan shrank tumours in about 37 percent of patients overall and 61 percent of those with the highest HER2 expression, leading to a tumour-agnostic approval.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-duo-e-jco-2023","kind":"paper","name":"DUO-E: durvalumab with carboplatin-paclitaxel and maintenance durvalumab with or without olaparib in advanced endometrial cancer","route":"/key-papers/paper-duo-e-jco-2023/","year":2024,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding durvalumab to first-line chemotherapy delayed progression in advanced endometrial cancer, and adding the PARP inhibitor olaparib to durvalumab maintenance helped further in mismatch repair-proficient tumours.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-ev-302-nejm-2024","kind":"paper","name":"EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer","route":"/key-papers/paper-ev-302-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Combining the Nectin-4 antibody-drug conjugate enfortumab vedotin with pembrolizumab nearly doubled survival compared with platinum chemotherapy in advanced urothelial cancer, the biggest advance in this disease in 40 years.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-ghai-california-poison-control-ivermectin-2024","kind":"paper","name":"Exposures to bleach, peroxide, disinfectants, antimalarials, and ivermectin reported to the California Poison Control System before and during the COVID-19 pandemic, 2015 to 2021","route":"/key-papers/paper-ghai-california-poison-control-ivermectin-2024/","year":2024,"journal":"Public Health 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placebo.","via":[{"id":"luspatercept","kind":"drug","name":"Luspatercept","route":"/drugs/luspatercept/"}]},{"id":"paper-keynote-942-lancet-2024","kind":"paper","name":"KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery","route":"/key-papers/paper-keynote-942-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"A vaccine custom-made from each patient's own tumour mutations, given with pembrolizumab after surgery for high-risk melanoma, reduced recurrence by about 44% compared with pembrolizumab alone in a mid-sized randomised trial, the first sign that personalised cancer vaccines can work.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-a18-os-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)","route":"/key-papers/paper-keynote-a18-os-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"The second report from KEYNOTE-A18 showed that adding pembrolizumab to chemoradiotherapy for high-risk locally advanced cervical cancer also lengthened life: 82.6% of women were alive at three years against 74.8%, a third fewer deaths.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-a18-pfs-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (progression-free survival)","route":"/key-papers/paper-keynote-a18-pfs-lancet-2024/","year":2024,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to standard chemoradiotherapy for high-risk locally advanced cervical cancer reduced progression or death by 30%, the first systemic advance in this setting since cisplatin was added to radiotherapy in 1999.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-nadina-nejm-2024","kind":"paper","name":"NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma","route":"/key-papers/paper-nadina-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Giving just two cycles of combination immunotherapy before removing melanoma lymph nodes cut relapses by more than two-thirds compared with a year of standard immunotherapy after surgery, and most patients needed no further treatment.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-niagara-nejm-2024","kind":"paper","name":"NIAGARA: durvalumab before and after cystectomy for muscle-invasive bladder cancer","route":"/key-papers/paper-niagara-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the immunotherapy durvalumab to chemotherapy before bladder removal, and continuing it afterwards, reduced relapse and death in muscle-invasive bladder cancer, the first improvement on neoadjuvant chemotherapy in two decades.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint 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before surgery clears dMMR colon cancer in most patients","route":"/key-papers/paper-niche-2-neoadjuvant-colon-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"translational","tldr":"In NICHE-2, four weeks of checkpoint blockade before surgery eliminated nearly all tumour in 95% of patients with mismatch-repair-deficient colon cancer, and none had relapsed at three years.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-perseus-dara-vrd-transplant-nejm-2024","kind":"paper","name":"PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma","route":"/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding daratumumab to the standard three-drug induction, transplant and maintenance cut progression or death by 58% and pushed MRD-negativity to three-quarters of patients.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-swog-s1826-nivolumab-avd-nejm-2024","kind":"paper","name":"SWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adults","route":"/key-papers/paper-swog-s1826-nivolumab-avd-nejm-2024/","year":2024,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding a PD-1 antibody to chemotherapy beat the brentuximab-based standard, with 92% of patients progression-free at two years and less nerve damage.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-atezolizumab-alveolar-soft-part-sarcoma-chen-nejm-2023","kind":"paper","name":"Atezolizumab for advanced alveolar soft part sarcoma","route":"/key-papers/paper-atezolizumab-alveolar-soft-part-sarcoma-chen-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"The PD-L1 antibody atezolizumab shrank tumours in about a quarter of patients with advanced alveolar soft part sarcoma, with responses lasting years in a disease resistant to chemotherapy, and became the first approved treatment for this sarcoma.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}]},{"id":"paper-cartitude-4-cilta-cel-nejm-2023","kind":"paper","name":"CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy","route":"/key-papers/paper-cartitude-4-cilta-cel-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Moving BCMA CAR-T to the second line cut the risk of progression or death by 74% compared with standard triplets, and later improved overall survival.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-checkmate-76k-nat-med-2023","kind":"paper","name":"CheckMate 76K: adjuvant nivolumab in resected stage IIB or IIC melanoma","route":"/key-papers/paper-checkmate-76k-nat-med-2023/","year":2023,"journal":"Nature Medicine","paperType":"rct","tldr":"Adjuvant nivolumab for a year after surgery cut the risk of recurrence by more than half in stage IIB and IIC melanoma, confirming the benefit seen with pembrolizumab in the same setting.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-codebreak-300-nejm-2023","kind":"paper","name":"CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer","route":"/key-papers/paper-codebreak-300-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Combining a KRAS G12C inhibitor with an EGFR antibody produced responses in about a quarter of patients with heavily pretreated KRAS G12C bowel cancer, versus none with standard chemotherapy, and more than doubled the time to progression.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-commands-luspatercept-mds-lancet-2023","kind":"paper","name":"COMMANDS: luspatercept versus epoetin alfa as first treatment for anaemia in lower-risk MDS needing transfusions","route":"/key-papers/paper-commands-luspatercept-mds-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"In COMMANDS, luspatercept, a drug that frees late-stage red cell production from TGF-beta-family braking, freed 59% of transfusion-dependent MDS patients from transfusions for at least 12 weeks, against 31% with the standard erythropoietin injection.","via":[{"id":"luspatercept","kind":"drug","name":"Luspatercept","route":"/drugs/luspatercept/"}]},{"id":"paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023","kind":"paper","name":"Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms","route":"/key-papers/paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023/","year":2023,"journal":"Breast Cancer Research","paperType":"observational","tldr":"In 232 Swedish early triple-negative cancers, half were PD-L1-positive by the atezolizumab test (SP142 IC 1%) but only 27% by the pembrolizumab threshold (22C3 CPS 10), and the two tests picked partly different patients.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-destiny-lung02-goto-jco-2023","kind":"paper","name":"DESTINY-Lung02: two doses of trastuzumab deruxtecan in HER2-mutant metastatic non-small-cell lung cancer","route":"/key-papers/paper-destiny-lung02-goto-jco-2023/","year":2023,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Comparing two doses of trastuzumab deruxtecan in HER2-mutant lung cancer showed that the lower 5.4 mg/kg dose gave the same response rate of about half with far less lung toxicity, fixing the approved dose.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-dreamseq-jco-2023","kind":"paper","name":"DREAMseq (ECOG-ACRIN EA6134): sequencing dabrafenib-trametinib and nivolumab-ipilimumab in BRAF-mutant metastatic melanoma","route":"/key-papers/paper-dreamseq-jco-2023/","year":2023,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Starting with nivolumab plus ipilimumab and switching to BRAF-MEK inhibitors at progression gave 20 percentage points better two-year survival than the reverse order in BRAF-mutant advanced melanoma, settling the question of which to use first.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-ck-301-101-jitc-2023","kind":"paper","name":"Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma","route":"/key-papers/paper-ck-301-101-jitc-2023/","year":2023,"journal":"Journal for ImmunoTherapy of Cancer","paperType":"observational","tldr":"The primary report of the metastatic cohort of CK-301-101: cosibelimab shrank tumours in 37 of 78 patients, most responses were still going at the cut-off, and severe immune side effects were uncommon.","via":[{"id":"cosibelimab","kind":"drug","name":"Cosibelimab","route":"/drugs/cosibelimab/"}]},{"id":"paper-glow-zolbetuximab-nat-med-2023","kind":"paper","name":"GLOW: zolbetuximab plus CAPOX in claudin 18.2-positive, HER2-negative gastric or gastro-oesophageal junction adenocarcinoma","route":"/key-papers/paper-glow-zolbetuximab-nat-med-2023/","year":2023,"journal":"Nature Medicine","paperType":"rct","tldr":"Adding the claudin 18.2 antibody zolbetuximab to CAPOX chemotherapy lengthened survival in claudin 18.2-positive advanced gastric cancer, confirming the SPOTLIGHT result with a different chemotherapy backbone.","via":[{"id":"zolbetuximab","kind":"drug","name":"Zolbetuximab","route":"/drugs/zolbetuximab/"}]},{"id":"paper-imbrave050-lancet-2023","kind":"paper","name":"IMbrave050: adjuvant atezolizumab plus bevacizumab versus active surveillance after resection or ablation of high-risk hepatocellular carcinoma","route":"/key-papers/paper-imbrave050-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"A year of atezolizumab plus bevacizumab after surgery or ablation for high-risk liver cancer initially reduced recurrences, but the benefit disappeared with longer follow-up, so there is still no proven adjuvant therapy.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-keynote-483-lancet-2023","kind":"paper","name":"KEYNOTE-483 (CCTG IND.227): pembrolizumab plus chemotherapy versus chemotherapy in untreated pleural mesothelioma","route":"/key-papers/paper-keynote-483-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to platinum-pemetrexed chemotherapy lengthened survival in untreated pleural mesothelioma by about a year in non-epithelioid tumours and by a smaller margin overall, giving a chemo-immunotherapy option alongside nivolumab-ipilimumab.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-811-janjigian-lancet-2023","kind":"paper","name":"KEYNOTE-811: pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma","route":"/key-papers/paper-keynote-811-janjigian-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to trastuzumab and chemotherapy improved response and progression-free survival in HER2-positive advanced gastric cancer, with the benefit concentrated in tumours that also express PD-L1.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-keynote-859-lancet-oncol-2023","kind":"paper","name":"KEYNOTE-859: pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer","route":"/key-papers/paper-keynote-859-lancet-oncol-2023/","year":2023,"journal":"The Lancet Oncology","paperType":"rct","tldr":"Adding pembrolizumab to platinum-fluoropyrimidine chemotherapy lengthened survival in HER2-negative advanced gastric cancer, with the largest gain in tumours with a PD-L1 combined positive score of 10 or more, confirming chemo-immunotherapy as first-line standard.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-966-lancet-2023","kind":"paper","name":"KEYNOTE-966: pembrolizumab plus gemcitabine and cisplatin for advanced biliary tract cancer","route":"/key-papers/paper-keynote-966-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to gemcitabine-cisplatin, with gemcitabine continued as maintenance, lengthened survival in advanced biliary tract cancer by about two months, confirming the role of chemo-immunotherapy shown by TOPAZ-1.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-krystal-1-crc-yaeger-nejm-2023","kind":"paper","name":"KRYSTAL-1: adagrasib with or without cetuximab in KRAS G12C-mutated colorectal cancer","route":"/key-papers/paper-krystal-1-crc-yaeger-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"The KRAS G12C inhibitor adagrasib on its own shrank about one in five previously treated colorectal cancers, but combined with the EGFR antibody cetuximab the response rate rose to nearly half, showing the two drugs are needed together in this disease.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-libretto-431-nejm-2023","kind":"paper","name":"LIBRETTO-431: first-line selpercatinib versus chemotherapy with or without pembrolizumab in RET fusion-positive lung cancer","route":"/key-papers/paper-libretto-431-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Given as first treatment, selpercatinib more than doubled the time to progression compared with platinum-pemetrexed chemotherapy plus pembrolizumab in RET fusion-positive lung cancer, and protected against brain metastases.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-patil-low-dose-nivolumab-jco-2023","kind":"paper","name":"Low-dose immunotherapy in head and neck cancer: a randomised study (Tata Memorial)","route":"/key-papers/paper-patil-low-dose-nivolumab-jco-2023/","year":2023,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Giving about one-twentieth of the standard dose of nivolumab alongside cheap oral chemotherapy nearly tripled one-year survival in advanced head and neck cancer, showing that immunotherapy can be made affordable without losing its effect.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-mountaineer-lancet-oncol-2023","kind":"paper","name":"MOUNTAINEER: tucatinib plus trastuzumab for HER2-positive, RAS wild-type metastatic colorectal cancer","route":"/key-papers/paper-mountaineer-lancet-oncol-2023/","year":2023,"journal":"The Lancet Oncology","paperType":"observational","tldr":"The chemotherapy-free combination of tucatinib and trastuzumab shrank tumours in almost four in ten patients with previously treated HER2-positive colorectal cancer, with responses lasting about a year, and became the first approved HER2 regimen for the disease.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-nrg-gy018-nejm-2023","kind":"paper","name":"NRG-GY018: pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer","route":"/key-papers/paper-nrg-gy018-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding pembrolizumab to carboplatin-paclitaxel and continuing it as maintenance cut the risk of progression by 70 percent in mismatch repair-deficient endometrial cancer and by 46 percent in mismatch repair-proficient disease.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-jimenez-gaona-ivermectin-loja-ecuador-2023","kind":"paper","name":"Outcome of ivermectin in cancer treatment: an experience in Loja, Ecuador","route":"/key-papers/paper-jimenez-gaona-ivermectin-loja-ecuador-2023/","year":2023,"journal":"Nursing Reports","paperType":"observational","tldr":"A survey in rural Ecuador found that about one in five people with cancer were taking cattle ivermectin alongside their treatment, while the specialists interviewed said there was no evidence and did not recommend it.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023","kind":"paper","name":"Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer","route":"/key-papers/paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023/","year":2023,"journal":"Annals of Oncology","paperType":"rct","tldr":"The UK trial that watched 161 women with early triple-negative breast cancer by three-monthly blood tests for tumour DNA: 27 percent tested positive within a year, but by then nearly three quarters already had visible metastases, and none of the five who started pembrolizumab cleared the DNA. The lesson was to test earlier and more sensitively.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-turner-c-trak-tn-ctdna-surveillance-ann-oncol-2023","kind":"paper","name":"Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer","route":"/key-papers/paper-turner-c-trak-tn-ctdna-surveillance-ann-oncol-2023/","year":2023,"journal":"Annals of Oncology","paperType":"rct","tldr":"The first trial to act on a positive ctDNA test in triple-negative cancer found that by the time three-monthly blood tests turned positive, seven in ten women already had visible metastases, and pembrolizumab cleared ctDNA in none of the five who received it.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023","kind":"paper","name":"Rojas 2023: a personalised mRNA vaccine trained T cells against each patient's pancreatic cancer, and those who responded stayed cancer-free longer","route":"/key-papers/paper-rojas-mrna-neoantigen-vaccine-pancreatic-nature-2023/","year":2023,"journal":"Nature","paperType":"translational","tldr":"Individualised mRNA vaccines encoding up to 20 of each patient's tumour mutations generated strong T-cell responses in half of pancreatic cancer patients after surgery, and those responders had far fewer relapses.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}]},{"id":"paper-ruby-nejm-2023","kind":"paper","name":"RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer","route":"/key-papers/paper-ruby-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the PD-1 antibody dostarlimab to first-line chemotherapy for advanced endometrial cancer cut progression by 72% in tumours with defective mismatch repair and by about a third overall, and later improved survival.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-xu-jama","kind":"paper","name":"Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial","route":"/key-papers/paper-xu-jama/","year":2023,"journal":"JAMA","paperType":"rct","tldr":"Paper cited by one trial page and one treatment page, indexed on Europe PMC as PubMed record 38051328 and published in JAMA; the citing pages link this DOI, which is how the record was matched.","via":[{"id":"sintilimab","kind":"drug","name":"Sintilimab","route":"/drugs/sintilimab/"}]},{"id":"paper-spotlight-lancet-2023","kind":"paper","name":"SPOTLIGHT: zolbetuximab, the first Claudin 18.2 antibody, added to chemotherapy in gastric cancer","route":"/key-papers/paper-spotlight-lancet-2023/","year":2023,"journal":"The Lancet","paperType":"rct","tldr":"In stomach cancers that express the protein Claudin 18.2, adding the antibody zolbetuximab to chemotherapy extended survival by nearly three months, making Claudin 18.2 a new biomarker to test for.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"paper-sunlight-nejm-2023","kind":"paper","name":"SUNLIGHT: trifluridine-tipiracil plus bevacizumab in refractory metastatic colorectal cancer","route":"/key-papers/paper-sunlight-nejm-2023/","year":2023,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding bevacizumab to the oral chemotherapy trifluridine-tipiracil lengthened survival by about three months in patients with colorectal cancer that had already been treated with two regimens, making the combination the standard third-line treatment.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-cercek-dostarlimab-rectal-nejm-2022","kind":"paper","name":"Cercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency","route":"/key-papers/paper-cercek-dostarlimab-rectal-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"translational","tldr":"All 12 patients with locally advanced dMMR rectal cancer had a complete clinical response to a PD-1 antibody alone, avoiding chemotherapy, radiotherapy and surgery.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-hoang-ivermectin-toxicity-clin-toxicol-2022","kind":"paper","name":"Characteristics of ivermectin toxicity in patients taking veterinary and human formulations for the prevention and treatment of COVID-19","route":"/key-papers/paper-hoang-ivermectin-toxicity-clin-toxicol-2022/","year":2022,"journal":"Clinical Toxicology","paperType":"observational","tldr":"An Oregon poison centre saw 37 people poisoned by ivermectin in six months of the pandemic; 30 had nervous-system effects, 21 were admitted to hospital and one died, with veterinary products giving the largest doses and the most confusion.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-checkmate-648-nejm-2022","kind":"paper","name":"CheckMate 648: nivolumab combination therapy in advanced oesophageal squamous cell carcinoma","route":"/key-papers/paper-checkmate-648-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding nivolumab to chemotherapy, or combining nivolumab with ipilimumab without chemotherapy, lengthened survival compared with chemotherapy alone in advanced oesophageal squamous cell carcinoma, with the largest gains in PD-L1-positive tumours.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-checkmate-816-nejm-2022","kind":"paper","name":"CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery","route":"/key-papers/paper-checkmate-816-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Just three cycles of chemotherapy with the immunotherapy nivolumab before surgery wiped out all viable tumour in a quarter of patients and reduced relapse or death by about a third, without making surgery harder.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-destiny-lung01-nejm-2022","kind":"paper","name":"DESTINY-Lung01: trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer","route":"/key-papers/paper-destiny-lung01-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Trastuzumab deruxtecan shrank tumours in more than half of patients with previously treated HER2-mutant lung cancer, a driver with no approved therapy until this study, though lung inflammation was a serious side effect.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-cercek-dmmr-rectal-nejm-2022","kind":"paper","name":"Dostarlimab alone cures mismatch-repair-deficient rectal cancer without surgery or radiotherapy","route":"/key-papers/paper-cercek-dmmr-rectal-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Six months of the PD-1 antibody dostarlimab made every tumour disappear in a small group of patients with mismatch-repair-deficient rectal cancer, allowing them to avoid chemotherapy, radiotherapy and surgery.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-empower-cervical-1-cemiplimab-nejm-2022","kind":"paper","name":"EMPOWER-Cervical 1: cemiplimab versus chemotherapy in recurrent cervical cancer after platinum","route":"/key-papers/paper-empower-cervical-1-cemiplimab-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The PD-1 antibody cemiplimab lengthened survival compared with single-agent chemotherapy in recurrent cervical cancer after platinum, regardless of PD-L1 expression, the first immunotherapy to show a survival benefit in this disease.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-himalaya-nejm-evidence-2022","kind":"paper","name":"HIMALAYA: tremelimumab plus durvalumab in unresectable hepatocellular carcinoma","route":"/key-papers/paper-himalaya-nejm-evidence-2022/","year":2022,"journal":"NEJM Evidence","paperType":"rct","tldr":"A single priming dose of the CTLA-4 antibody tremelimumab followed by durvalumab lengthened survival compared with sorafenib in advanced liver cancer without the bleeding risk of bevacizumab, giving a second first-line immunotherapy standard.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"tremelimumab","kind":"drug","name":"Tremelimumab","route":"/drugs/tremelimumab/"}]},{"id":"paper-keynote-355-nejm-2022","kind":"paper","name":"KEYNOTE-355: pembrolizumab plus chemotherapy for PD-L1-positive advanced triple-negative breast cancer","route":"/key-papers/paper-keynote-355-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding pembrolizumab to first-line chemotherapy lengthened survival by almost seven months in advanced triple-negative breast cancer whose tumours had a PD-L1 combined positive score of 10 or more.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-522-nejm-2022","kind":"paper","name":"KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer","route":"/key-papers/paper-keynote-522-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the immunotherapy pembrolizumab to chemotherapy before surgery, then continuing it afterwards, cut the risk of relapse or death by about a third in stage II-III triple-negative breast cancer and later improved survival.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-716-lancet-2022","kind":"paper","name":"KEYNOTE-716: adjuvant pembrolizumab versus placebo in completely resected stage IIB or IIC melanoma","route":"/key-papers/paper-keynote-716-lancet-2022/","year":2022,"journal":"The Lancet","paperType":"rct","tldr":"A year of pembrolizumab after surgery for stage IIB or IIC melanoma reduced recurrences and distant metastases by about 35 to 40 percent, extending adjuvant immunotherapy to node-negative but thick or ulcerated melanomas.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-775-nejm-2022","kind":"paper","name":"KEYNOTE-775: lenvatinib plus pembrolizumab versus chemotherapy for previously treated advanced endometrial cancer","route":"/key-papers/paper-keynote-775-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"After platinum chemotherapy, the combination of the kinase inhibitor lenvatinib and pembrolizumab lengthened survival compared with doxorubicin or paclitaxel in advanced endometrial cancer, including in the mismatch repair-proficient majority.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-gross-neoadjuvant-cemiplimab-cscc-nejm-2022","kind":"paper","name":"Neoadjuvant cemiplimab for stage II to IV cutaneous squamous cell carcinoma","route":"/key-papers/paper-gross-neoadjuvant-cemiplimab-cscc-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Giving four doses of cemiplimab before surgery for resectable cutaneous squamous cell carcinoma eliminated all viable tumour in half of patients and left only minimal residual disease in another 13 percent, opening the way to smaller operations and less radiotherapy.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-polarix-polatuzumab-rchp-nejm-2022","kind":"paper","name":"POLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphoma","route":"/key-papers/paper-polarix-polatuzumab-rchp-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Replacing one chemotherapy drug in R-CHOP with a CD79b antibody-drug conjugate modestly reduced progression (2-year PFS 76.7% versus 70.2%) without changing survival or side effects.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-relativity-047-nejm-2022","kind":"paper","name":"RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma","route":"/key-papers/paper-relativity-047-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding an antibody against a second immune brake, LAG-3, to nivolumab delayed progression in advanced melanoma compared with nivolumab alone, with far fewer serious side effects than the ipilimumab combination.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-rohaas-til-vs-ipilimumab-nejm-2022","kind":"paper","name":"Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma","route":"/key-papers/paper-rohaas-til-vs-ipilimumab-nejm-2022/","year":2022,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In a head-to-head trial, tumour-infiltrating lymphocyte therapy halved the risk of progression compared with ipilimumab in melanoma that had mostly already failed PD-1 blockade.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"}]},{"id":"paper-ishiguro-dichloroacetate-ivermectin-cureus-2022","kind":"paper","name":"Synergistic anti-tumor effect of dichloroacetate and ivermectin","route":"/key-papers/paper-ishiguro-dichloroacetate-ivermectin-cureus-2022/","year":2022,"journal":"Cureus","paperType":"observational","tldr":"Three patients treated at a private clinic with dichloroacetate, omeprazole, tamoxifen and ivermectin were reported to have relief of symptoms; there was no control, no measured tumour response and no follow-up study.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-topaz-1-nejm-evidence-2022","kind":"paper","name":"TOPAZ-1: durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer","route":"/key-papers/paper-topaz-1-nejm-evidence-2022/","year":2022,"journal":"NEJM Evidence","paperType":"rct","tldr":"Adding durvalumab to gemcitabine-cisplatin lengthened survival in advanced bile duct and gallbladder cancer, the first improvement on chemotherapy alone in more than a decade, with about a quarter of patients alive at two years.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"paper-tuxedo-1-trastuzumab-deruxtecan-brain-metastases-nat-med-2022","kind":"paper","name":"TUXEDO-1: trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastases","route":"/key-papers/paper-tuxedo-1-trastuzumab-deruxtecan-brain-metastases-nat-med-2022/","year":2022,"journal":"Nature Medicine","paperType":"observational","tldr":"In a small trial, the antibody-drug conjugate trastuzumab deruxtecan shrank brain metastases in almost three quarters of women with HER2-positive breast cancer, showing that a large antibody-based drug can work inside the brain.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-asco-pembrolizumab-early-tnbc-rapid-update-jco-2022","kind":"paper","name":"Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-Risk, Early-Stage Triple-Negative Breast Cancer: ASCO Guideline Rapid Recommendation Update","route":"/key-papers/paper-asco-pembrolizumab-early-tnbc-rapid-update-jco-2022/","year":2022,"journal":"Journal of Clinical Oncology","paperType":"guideline","tldr":"The 2022 fast-track amendment in which the US oncology society added pembrolizumab before and after surgery for high-risk early triple-negative breast cancer, a year after its main guideline had said the evidence was insufficient.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint 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specialists.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-raghav-atezolizumab-bevacizumab-peritoneal-mesothelioma-cancer-discov-2021","kind":"paper","name":"Atezolizumab plus bevacizumab in advanced malignant peritoneal mesothelioma","route":"/key-papers/paper-raghav-atezolizumab-bevacizumab-peritoneal-mesothelioma-cancer-discov-2021/","year":2021,"journal":"Cancer Discovery","paperType":"observational","tldr":"In a small trial combining PD-L1 and VEGF blockade, four in ten patients with previously treated peritoneal mesothelioma responded, with responses lasting well over a year, the first dedicated prospective evidence for immunotherapy in this rare disease.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-ux023t-cl201-jan-de-beur-jbmr-2021","kind":"paper","name":"Burosumab for the treatment of tumor-induced osteomalacia (UX023T-CL201)","route":"/key-papers/paper-ux023t-cl201-jan-de-beur-jbmr-2021/","year":2021,"journal":"Journal of Bone and Mineral Research","paperType":"observational","tldr":"In 14 adults whose bones had softened because a hidden tumour was making them lose phosphate, blocking the hormone responsible brought blood phosphate back to normal for nearly three years and let a third of their fractures heal fully.","via":[{"id":"burosumab","kind":"drug","name":"Burosumab","route":"/drugs/burosumab/"}]},{"id":"paper-captain-1st-camrelizumab-chemotherapy-npc-lancet-oncol-2021","kind":"paper","name":"CAPTAIN-1st: camrelizumab versus placebo with gemcitabine and cisplatin as 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cemiplimab shrank tumours in about three in ten, giving a second-line option where none existed.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-checkmate-577-nejm-2021","kind":"paper","name":"CheckMate 577: adjuvant nivolumab in resected oesophageal or gastro-oesophageal junction cancer","route":"/key-papers/paper-checkmate-577-nejm-2021/","year":2021,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A year of nivolumab after chemoradiotherapy and surgery doubled disease-free survival in patients with oesophageal or junctional cancer who still had residual tumour at surgery, the first adjuvant therapy to work in this setting.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-checkmate-649-lancet-2021","kind":"paper","name":"CheckMate 649: nivolumab plus chemotherapy as first treatment for advanced gastric, gastro-oesophageal junction and oesophageal 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survival compared with platinum-pemetrexed chemotherapy in pleural mesothelioma, the first improvement in first-line treatment in almost twenty years, with the largest gain in non-epithelioid tumours.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-clear-nejm-2021","kind":"paper","name":"CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer","route":"/key-papers/paper-clear-nejm-2021/","year":2021,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Combining the multi-kinase inhibitor lenvatinib with pembrolizumab more than doubled the time to progression compared with sunitinib in advanced clear-cell kidney cancer and improved survival, with 71% of patients responding.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-destiny-crc01-lancet-oncol-2021","kind":"paper","name":"DESTINY-CRC01: trastuzumab deruxtecan in HER2-expressing metastatic colorectal cancer","route":"/key-papers/paper-destiny-crc01-lancet-oncol-2021/","year":2021,"journal":"The Lancet Oncology","paperType":"observational","tldr":"Trastuzumab deruxtecan shrank tumours in about 45 percent of patients with HER2-high colorectal cancer, including those who had already received other HER2 drugs, but did nothing for tumours with low HER2 expression and carried a risk of lung inflammation.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-figo-cancer-report-gestational-trophoblastic-disease-ijgo-2021","kind":"paper","name":"FIGO Cancer Report 2021: diagnosis and management of gestational trophoblastic disease","route":"/key-papers/paper-figo-cancer-report-gestational-trophoblastic-disease-ijgo-2021/","year":2021,"journal":"International Journal of Gynecology & Obstetrics","paperType":"guideline","tldr":"The FIGO review of trophoblastic disease from molar pregnancy to choriocarcinoma and the rare placental-site and epithelioid tumours: hCG surveillance, the risk score, single-agent or EMA/CO chemotherapy, surgery, and immunotherapy for resistant disease.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-draganov-ivermectin-cold-tumours-npj-breast-cancer-2021","kind":"paper","name":"Ivermectin converts cold tumors hot and synergizes with 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The journal has since flagged duplicated images in one figure and the raw data are gone.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-tang-ivermectin-potential-anticancer-pharmacol-res-2021","kind":"paper","name":"Ivermectin, a potential anticancer drug derived from an antiparasitic drug","route":"/key-papers/paper-tang-ivermectin-potential-anticancer-pharmacol-res-2021/","year":2021,"journal":"Pharmacological Research","paperType":"review","tldr":"A 2021 review of the pathways through which ivermectin killed cancer cells in the laboratory, written as a case for testing it in people.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-jupiter-02-toripalimab-chemotherapy-npc-nat-med-2021","kind":"paper","name":"JUPITER-02: toripalimab or 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cancer","route":"/key-papers/paper-keynote-590-lancet-2021/","year":2021,"journal":"The Lancet","paperType":"rct","tldr":"Adding pembrolizumab to cisplatin-fluorouracil lengthened survival in advanced oesophageal cancer of both histologies, most clearly in squamous cell carcinoma and in tumours with high PD-L1, establishing chemo-immunotherapy as the first-line standard.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-826-nejm-2021","kind":"paper","name":"KEYNOTE-826: pembrolizumab plus chemotherapy with or without bevacizumab for persistent, recurrent or metastatic cervical cancer","route":"/key-papers/paper-keynote-826-nejm-2021/","year":2021,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding pembrolizumab to first-line chemotherapy, with or without bevacizumab, lengthened survival in advanced cervical cancer, the first improvement in the disease since bevacizumab was added seven years earlier.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-rugo-impassion130-pdl1-assay-comparison-jnci-2021","kind":"paper","name":"PD-L1 immunohistochemistry assay comparison in atezolizumab plus nab-paclitaxel-treated advanced triple-negative breast cancer","route":"/key-papers/paper-rugo-impassion130-pdl1-assay-comparison-jnci-2021/","year":2021,"journal":"JNCI: Journal of the National Cancer Institute","paperType":"translational","tldr":"The same 614 IMpassion130 tumours were PD-L1-positive in 46% with the SP142 test the trial used but in 73 to 75% with the 22C3 and SP263 tests, and the atezolizumab benefit lived in the SP142-positive tumours, so the assays cannot be swapped.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}]},{"id":"paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021","kind":"paper","name":"PD-L1 Immunohistochemistry Assay Comparison in 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year.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"}]},{"id":"paper-her2climb-brain-lin-jco-2020","kind":"paper","name":"HER2CLIMB brain metastases analysis: intracranial efficacy and survival with tucatinib","route":"/key-papers/paper-her2climb-brain-lin-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Among the HER2CLIMB patients with brain metastases, tucatinib doubled the intracranial response rate, cut the risk of intracranial progression or death by about two thirds and lengthened survival.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-her2climb-nejm-2020","kind":"paper","name":"HER2CLIMB: tucatinib with trastuzumab and capecitabine for HER2-positive metastatic breast cancer, including brain metastases","route":"/key-papers/paper-her2climb-nejm-2020/","year":2020,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the brain-penetrant HER2 pill tucatinib to trastuzumab and capecitabine lengthened survival in heavily pretreated HER2-positive metastatic breast cancer, and uniquely the trial included patients with active brain metastases, who also benefited.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-imbrave150-nejm-2020","kind":"paper","name":"IMbrave150: atezolizumab plus bevacizumab replaces sorafenib as first treatment for advanced liver cancer","route":"/key-papers/paper-imbrave150-nejm-2020/","year":2020,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Combining the immunotherapy atezolizumab with the anti-blood-vessel antibody bevacizumab helped patients with advanced hepatocellular carcinoma live longer than sorafenib, ending a decade in which nothing had beaten that drug.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-javelin-bladder-100-nejm-2020","kind":"paper","name":"JAVELIN Bladder 100: avelumab maintenance after first-line platinum chemotherapy in advanced urothelial cancer","route":"/key-papers/paper-javelin-bladder-100-nejm-2020/","year":2020,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Continuing with the immunotherapy avelumab after chemotherapy had controlled advanced bladder cancer lengthened survival by about seven months compared with watching and waiting.","via":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"}]},{"id":"paper-keynote-062-shitara-jama-oncol-2020","kind":"paper","name":"KEYNOTE-062: pembrolizumab or pembrolizumab plus chemotherapy versus chemotherapy in PD-L1-positive advanced gastric cancer","route":"/key-papers/paper-keynote-062-shitara-jama-oncol-2020/","year":2020,"journal":"JAMA Oncology","paperType":"rct","tldr":"In first-line PD-L1-positive gastric cancer, pembrolizumab alone was no worse than chemotherapy for survival but did not beat it, and adding it to chemotherapy did not help either; the exception was microsatellite-unstable tumours, which did dramatically better with pembrolizumab.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020","kind":"paper","name":"KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer","route":"/key-papers/paper-keynote-158-pembrolizumab-msi-high-noncolorectal-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Pembrolizumab shrank tumours in about a third of patients with mismatch repair-deficient cancers of many different organs, with responses that often lasted years; the pancreatic cancer group responded less often than most. It is the trial behind the tissue-agnostic approval for MSI-high cancer.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-177-nejm-2020","kind":"paper","name":"KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer","route":"/key-papers/paper-keynote-177-nejm-2020/","year":2020,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"For the roughly 5% of metastatic bowel cancers with defective DNA mismatch repair, pembrolizumab alone lengthened the time without progression compared with chemotherapy, with far fewer severe side effects, and 83% of responses lasted two years or more. It made first-line pembrolizumab the standard for this group.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-629-pembrolizumab-cscc-grob-jco-2020","kind":"paper","name":"KEYNOTE-629: pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma","route":"/key-papers/paper-keynote-629-pembrolizumab-cscc-grob-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Pembrolizumab shrank tumours in about a third of patients with recurrent or metastatic cutaneous squamous cell carcinoma, with most responses lasting beyond a year, leading to its approval as an alternative to cemiplimab.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-trophimmun-avelumab-chemoresistant-gtn-jco-2020","kind":"paper","name":"TROPHIMMUN cohort A: avelumab in gestational trophoblastic tumours resistant to single-agent chemotherapy","route":"/key-papers/paper-trophimmun-avelumab-chemoresistant-gtn-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"The first trial of immunotherapy in gestational trophoblastic disease found that the PD-L1 antibody avelumab cured about half of women whose tumours had stopped responding to a single chemotherapy drug, sparing them combination chemotherapy.","via":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"}]},{"id":"paper-trophimmun-avelumab-chemoresistant-gtn-you-jco-2020","kind":"paper","name":"TROPHIMMUN cohort A: avelumab in gestational trophoblastic tumours resistant to single-agent chemotherapy","route":"/key-papers/paper-trophimmun-avelumab-chemoresistant-gtn-you-jco-2020/","year":2020,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"The PD-L1 antibody avelumab cured about half of women whose gestational trophoblastic tumour had stopped responding to single-drug chemotherapy, with mild side effects.","via":[{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"}]},{"id":"paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020","kind":"paper","name":"Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer","route":"/key-papers/paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020/","year":2020,"journal":"Clinical Cancer Research","paperType":"observational","tldr":"In 62 women with metastatic triple-negative cancer treated with immunotherapy, high mutation burden (18%) went with a year of progression-free time versus under four months, while PTEN loss (29%) went with almost no responses.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-augment-lenalidomide-rituximab-leonard-jco-2019","kind":"paper","name":"AUGMENT: lenalidomide plus rituximab versus rituximab alone in relapsed indolent lymphoma","route":"/key-papers/paper-augment-lenalidomide-rituximab-leonard-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding lenalidomide to rituximab more than doubled the time to progression in relapsed follicular and marginal zone lymphoma compared with rituximab alone, establishing a chemotherapy-free option for relapsed indolent lymphoma.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-beacon-crc-kopetz-nejm-2019","kind":"paper","name":"BEACON CRC: encorafenib and cetuximab with or without binimetinib in BRAF V600E-mutated colorectal cancer","route":"/key-papers/paper-beacon-crc-kopetz-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Blocking BRAF with encorafenib and EGFR with cetuximab lengthened survival compared with standard chemotherapy in previously treated BRAF V600E-mutant colorectal cancer, the first targeted regimen to work in this poor-prognosis group.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-cassiopeia-lancet-2019","kind":"paper","name":"CASSIOPEIA: daratumumab added to bortezomib, thalidomide and dexamethasone before and after transplant in newly diagnosed myeloma","route":"/key-papers/paper-cassiopeia-lancet-2019/","year":2019,"journal":"The Lancet","paperType":"rct","tldr":"Adding the antibody daratumumab to a standard three-drug induction and consolidation around autologous transplant deepened responses and delayed progression in newly diagnosed myeloma, establishing four-drug induction.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-cll14-venetoclax-obinutuzumab-nejm-2019","kind":"paper","name":"CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients","route":"/key-papers/paper-cll14-venetoclax-obinutuzumab-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A fixed one-year course of two targeted drugs kept CLL under control far longer than chemo-immunotherapy, and most patients had no detectable disease when treatment stopped.","via":[{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"}]},{"id":"paper-de-escalate-lancet-2019","kind":"paper","name":"De-ESCALaTE HPV: radiotherapy plus cisplatin or cetuximab in low-risk HPV-positive oropharyngeal cancer","route":"/key-papers/paper-de-escalate-lancet-2019/","year":2019,"journal":"The Lancet","paperType":"rct","tldr":"This European trial, like its American counterpart, found that replacing cisplatin with cetuximab in low-risk HPV-positive oropharyngeal cancer caused more recurrences and deaths without reducing severe toxicity.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-katherine-nejm-2019","kind":"paper","name":"KATHERINE: switching to T-DM1 when HER2-positive breast cancer survives pre-surgery treatment","route":"/key-papers/paper-katherine-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Women whose HER2-positive breast cancer was still present at surgery after chemotherapy and trastuzumab had half the risk of relapse if their post-surgery treatment was switched to the antibody-drug conjugate T-DM1 instead of continuing trastuzumab.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-keynote-048-lancet-2019","kind":"paper","name":"KEYNOTE-048: pembrolizumab, alone or with chemotherapy, as first treatment for recurrent or metastatic head and neck cancer","route":"/key-papers/paper-keynote-048-lancet-2019/","year":2019,"journal":"The Lancet","paperType":"rct","tldr":"Pembrolizumab, either alone in PD-L1-positive tumours or combined with chemotherapy, helped patients with recurrent or metastatic head and neck squamous cell cancer live longer than the previous cetuximab-based standard.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-keynote-170-pembrolizumab-pmbcl-armand-jco-2019","kind":"paper","name":"KEYNOTE-170: pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma","route":"/key-papers/paper-keynote-170-pembrolizumab-pmbcl-armand-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Pembrolizumab produced responses in about 45 percent of patients with primary mediastinal B-cell lymphoma that had relapsed after chemotherapy, a lymphoma whose frequent 9p24.1 amplification makes it unusually sensitive to PD-1 blockade.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-426-nejm-2019","kind":"paper","name":"KEYNOTE-426: pembrolizumab plus axitinib versus sunitinib for advanced renal cell carcinoma","route":"/key-papers/paper-keynote-426-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Combining pembrolizumab with the kinase inhibitor axitinib lengthened survival and delayed progression compared with sunitinib as first treatment for advanced clear cell kidney cancer, across all risk groups.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-maia-daratumumab-rd-nejm-2019","kind":"paper","name":"MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant","route":"/key-papers/paper-maia-daratumumab-rd-nejm-2019/","year":2019,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the CD38 antibody daratumumab to standard lenalidomide-dexamethasone cut the risk of progression or death by about 44% in older myeloma patients, and later extended survival.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"paper-rtog-1016-lancet-2019","kind":"paper","name":"NRG Oncology RTOG 1016: radiotherapy plus cetuximab versus cisplatin in HPV-positive oropharyngeal cancer","route":"/key-papers/paper-rtog-1016-lancet-2019/","year":2019,"journal":"The Lancet","paperType":"rct","tldr":"Trying to reduce toxicity by swapping cisplatin for cetuximab during radiotherapy in HPV-positive oropharyngeal cancer backfired: cetuximab gave worse survival and more recurrences with no reduction in toxicity, so cisplatin remains standard.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-takahashi-trastuzumab-docetaxel-salivary-duct-jco-2019","kind":"paper","name":"Phase 2 trial of trastuzumab and docetaxel in HER2-positive salivary duct carcinoma","route":"/key-papers/paper-takahashi-trastuzumab-docetaxel-salivary-duct-jco-2019/","year":2019,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"In HER2-positive salivary duct carcinoma, an aggressive salivary cancer resembling breast cancer, trastuzumab plus docetaxel shrank tumours in 70 percent of patients, establishing HER2 testing and targeting in the disease.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-binnewies-tumor-immune-microenvironment-natmed-2018","kind":"paper","name":"Binnewies 2018: understanding the tumour immune microenvironment for effective therapy","route":"/key-papers/paper-binnewies-tumor-immune-microenvironment-natmed-2018/","year":2018,"journal":"Nature Medicine","paperType":"review","tldr":"A review that sorted tumours by where their immune cells sit, inflamed and infiltrated, infiltrated but excluded, or immune-poor, and argued that this classification should guide which immunotherapy a patient receives.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-fader-trastuzumab-uterine-serous-jco-2018","kind":"paper","name":"Carboplatin-paclitaxel with or without trastuzumab in HER2-positive advanced or recurrent uterine serous carcinoma","route":"/key-papers/paper-fader-trastuzumab-uterine-serous-jco-2018/","year":2018,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding trastuzumab to chemotherapy for HER2-positive uterine serous carcinoma, an aggressive endometrial cancer, lengthened progression-free survival by about four months and later showed a survival benefit, making HER2 testing routine in this subtype.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-checkmate-205-nivolumab-rr-hodgkin-extended-follow-up-jco-2018","kind":"paper","name":"CheckMate 205: nivolumab for relapsed or refractory classical Hodgkin lymphoma after autologous transplant failure, extended follow-up","route":"/key-papers/paper-checkmate-205-nivolumab-rr-hodgkin-extended-follow-up-jco-2018/","year":2018,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"The PD-1 antibody nivolumab produced responses in about seven in ten patients whose Hodgkin lymphoma had returned after a stem cell transplant, with responses lasting well over a year, confirming the exquisite sensitivity of this lymphoma to checkpoint blockade.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-checkmate-214-nejm-2018","kind":"paper","name":"CheckMate 214: nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma","route":"/key-papers/paper-checkmate-214-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Dual immunotherapy with nivolumab and ipilimumab lengthened survival compared with sunitinib in intermediate- and poor-risk advanced kidney cancer, with about one in ten patients achieving a complete response that has proved durable over years.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018","kind":"paper","name":"Hu 2018: evaluating mismatch repair deficiency in pancreatic adenocarcinoma, challenges and recommendations","route":"/key-papers/paper-hu-mismatch-repair-deficiency-pancreatic-adenocarcinoma-ccr-2018/","year":2018,"journal":"Clinical Cancer Research","paperType":"observational","tldr":"Of more than 800 pancreatic cancers sequenced at one centre, under one in a hundred were mismatch repair deficient, most in people with Lynch syndrome, and several responded to immunotherapy. The paper set out how to test for the abnormality reliably in a cancer where standard tests often mislead.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-054-eggermont-nejm-2018","kind":"paper","name":"KEYNOTE-054 (EORTC 1325): adjuvant pembrolizumab versus placebo in resected stage III melanoma","route":"/key-papers/paper-keynote-054-eggermont-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A year of pembrolizumab after surgery for stage III melanoma cut the risk of recurrence by 43 percent compared with placebo, the first placebo-controlled proof that adjuvant PD-1 blockade works.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-189-nejm-2018","kind":"paper","name":"KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation","route":"/key-papers/paper-keynote-189-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding pembrolizumab to standard chemotherapy roughly halved the risk of death in newly diagnosed non-squamous lung cancer, whatever the PD-L1 level, making chemo-immunotherapy the default first treatment.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-mavoric-mogamulizumab-lancet-oncol-2018","kind":"paper","name":"MAVORIC: mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma","route":"/key-papers/paper-mavoric-mogamulizumab-lancet-oncol-2018/","year":2018,"journal":"The Lancet Oncology","paperType":"rct","tldr":"The anti-CCR4 antibody mogamulizumab doubled the time to progression compared with vorinostat in previously treated mycosis fungoides and Sezary syndrome, with particularly strong activity in the blood, and became the first antibody approved for these lymphomas.","via":[{"id":"mogamulizumab","kind":"drug","name":"Mogamulizumab","route":"/drugs/mogamulizumab/"}]},{"id":"paper-murano-venetoclax-rituximab-nejm-2018","kind":"paper","name":"MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL","route":"/key-papers/paper-murano-venetoclax-rituximab-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In relapsed CLL, a time-limited venetoclax-rituximab course cut progression risk by more than 80% compared with bendamustine-rituximab and later improved survival.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-empower-cscc-1-cemiplimab-migden-nejm-2018","kind":"paper","name":"PD-1 blockade with cemiplimab in advanced cutaneous squamous cell carcinoma (EMPOWER-CSCC-1)","route":"/key-papers/paper-empower-cscc-1-cemiplimab-migden-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Cemiplimab shrank tumours in about half of patients with metastatic or locally advanced cutaneous squamous cell carcinoma, a highly mutated skin cancer with almost no previous treatment options, leading to the first approval for the disease.","via":[{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"}]},{"id":"paper-giaccone-pembrolizumab-thymic-carcinoma-lancet-oncol-2018","kind":"paper","name":"Pembrolizumab in patients with thymic carcinoma: a single-arm phase 2 study","route":"/key-papers/paper-giaccone-pembrolizumab-thymic-carcinoma-lancet-oncol-2018/","year":2018,"journal":"The Lancet Oncology","paperType":"observational","tldr":"Immunotherapy shrank thymic carcinoma in about one patient in five after chemotherapy, but caused severe immune attacks on the heart and muscle more often than in other cancers, so it is used with care.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-relevance-rituximab-lenalidomide-follicular-lymphoma-morschhauser-nejm-2018","kind":"paper","name":"RELEVANCE: rituximab plus lenalidomide in advanced untreated follicular lymphoma","route":"/key-papers/paper-relevance-rituximab-lenalidomide-follicular-lymphoma-morschhauser-nejm-2018/","year":2018,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A chemotherapy-free combination of rituximab and lenalidomide worked as well as rituximab with chemotherapy for untreated follicular lymphoma, though not better, with different side effects.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-ribas-wolchok-checkpoint-blockade-science-2018","kind":"paper","name":"Ribas and Wolchok 2018: cancer immunotherapy using checkpoint blockade","route":"/key-papers/paper-ribas-wolchok-checkpoint-blockade-science-2018/","year":2018,"journal":"Science","paperType":"review","tldr":"A review by two of the field's leading trialists, written as checkpoint inhibitors reached a dozen cancers, explaining how CTLA-4 and PD-1 blockade work, why only some patients respond, and how resistance arises.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-juarez-ivermectin-repositioned-cancer-drug-2018","kind":"paper","name":"The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug","route":"/key-papers/paper-juarez-ivermectin-repositioned-cancer-drug-2018/","year":2018,"journal":"American Journal of Cancer Research","paperType":"review","tldr":"A 2018 review that gathered the cell-culture and animal experiments on ivermectin and argued it was ready for cancer trials; those trials began five years later and have not reported.","via":[{"id":"ivermectin","kind":"drug","name":"Ivermectin","route":"/drugs/ivermectin/"}]},{"id":"paper-thorsson-immune-landscape-of-cancer-immunity-2018","kind":"paper","name":"Thorsson 2018: the immune landscape of cancer across 10,000 tumours","route":"/key-papers/paper-thorsson-immune-landscape-of-cancer-immunity-2018/","year":2018,"journal":"Immunity","paperType":"translational","tldr":"An analysis of more than 10,000 tumours from 33 cancer types in The Cancer Genome Atlas that sorted cancers into six immune subtypes, showing that the immune environment of a tumour cuts across its tissue of origin and affects prognosis.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-anbl1221-irinotecan-temozolomide-dinutuximab-mody-lancet-oncol-2017","kind":"paper","name":"ANBL1221: irinotecan-temozolomide with temsirolimus or dinutuximab in relapsed or refractory neuroblastoma","route":"/key-papers/paper-anbl1221-irinotecan-temozolomide-dinutuximab-mody-lancet-oncol-2017/","year":2017,"journal":"The Lancet Oncology","paperType":"rct","tldr":"In children whose neuroblastoma had come back, adding the anti-GD2 antibody dinutuximab to irinotecan and temozolomide shrank the cancer in half of them, while adding temsirolimus almost never did.","via":[{"id":"dinutuximab","kind":"drug","name":"Dinutuximab (ch14.18) / dinutuximab beta","route":"/drugs/dinutuximab/"}]},{"id":"paper-aphinity-nejm-2017","kind":"paper","name":"APHINITY: adjuvant pertuzumab added to trastuzumab and chemotherapy in early HER2-positive breast cancer","route":"/key-papers/paper-aphinity-nejm-2017/","year":2017,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding a second HER2 antibody, pertuzumab, to a year of trastuzumab after surgery reduced recurrences modestly in early HER2-positive breast cancer, with the gain concentrated in women with lymph node involvement.","via":[{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-checkmate-238-nejm-2017","kind":"paper","name":"CheckMate 238: adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma","route":"/key-papers/paper-checkmate-238-nejm-2017/","year":2017,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"A year of adjuvant nivolumab after surgery for high-risk melanoma reduced recurrences more than the previous standard, high-dose ipilimumab, with a quarter of the severe toxicity, making PD-1 blockade the adjuvant standard.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-gallium-obinutuzumab-first-line-follicular-lymphoma-marcus-nejm-2017","kind":"paper","name":"GALLIUM: obinutuzumab for the first-line treatment of follicular lymphoma","route":"/key-papers/paper-gallium-obinutuzumab-first-line-follicular-lymphoma-marcus-nejm-2017/","year":2017,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Obinutuzumab with chemotherapy and as maintenance kept follicular lymphoma from progressing for longer than rituximab, at the cost of more serious side effects.","via":[{"id":"obinutuzumab","kind":"drug","name":"Obinutuzumab","route":"/drugs/obinutuzumab/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-le-mmr-deficiency-science-2017","kind":"paper","name":"Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval","route":"/key-papers/paper-le-mmr-deficiency-science-2017/","year":2017,"journal":"Science","paperType":"translational","tldr":"Across 86 patients with 12 different dMMR cancers, pembrolizumab produced responses in 53% and complete responses in 21%, prompting the first approval of a cancer drug based on a genetic marker rather than tumour site.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-nci9673-nivolumab-metastatic-anal-cancer-morris-lancet-oncol-2017","kind":"paper","name":"NCI9673: nivolumab for previously treated unresectable metastatic anal cancer","route":"/key-papers/paper-nci9673-nivolumab-metastatic-anal-cancer-morris-lancet-oncol-2017/","year":2017,"journal":"The Lancet Oncology","paperType":"observational","tldr":"In the first completed immunotherapy trial for anal cancer, the PD-1 antibody nivolumab shrank tumours in a quarter of heavily pretreated patients with few side effects.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-dangelo-mucosal-melanoma-pooled-jco-2017","kind":"paper","name":"Nivolumab alone or with ipilimumab in mucosal melanoma: pooled analysis","route":"/key-papers/paper-dangelo-mucosal-melanoma-pooled-jco-2017/","year":2017,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"Pooling several trials showed that mucosal melanoma responds to nivolumab less often than skin melanoma, but that adding ipilimumab raised the response rate from about a quarter to more than a third, supporting combination immunotherapy first.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-pacific-nejm-2017","kind":"paper","name":"PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer","route":"/key-papers/paper-pacific-nejm-2017/","year":2017,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Giving the immunotherapy durvalumab for a year after chemoradiotherapy for unresectable stage III lung cancer tripled the time to progression and raised five-year survival from about a third to over 40%.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-ptld-1-risk-stratified-sequential-treatment-trappe-jco-2017","kind":"paper","name":"PTLD-1: response to rituximab induction as a predictive marker allowing stratification into rituximab or R-CHOP consolidation in B-cell post-transplant lymphoproliferative disorder","route":"/key-papers/paper-ptld-1-risk-stratified-sequential-treatment-trappe-jco-2017/","year":2017,"journal":"Journal of Clinical Oncology","paperType":"observational","tldr":"In lymphoma arising after an organ transplant, starting with rituximab alone and then choosing between more rituximab and chemotherapy by response gave complete remission in seven of ten patients and a median survival of more than six years.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-sarc028-pembrolizumab-sarcoma-tawbi-lancet-oncol-2017","kind":"paper","name":"SARC028: pembrolizumab in advanced soft tissue and bone sarcoma","route":"/key-papers/paper-sarc028-pembrolizumab-sarcoma-tawbi-lancet-oncol-2017/","year":2017,"journal":"The Lancet Oncology","paperType":"observational","tldr":"Pembrolizumab had little effect in most sarcomas, but it shrank tumours in about 40 percent of patients with undifferentiated pleomorphic sarcoma and some with dedifferentiated liposarcoma, singling out these subtypes for immunotherapy.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-checkmate-141-ferris-nejm-2016","kind":"paper","name":"CheckMate 141: nivolumab for recurrent head and neck squamous cell carcinoma after platinum","route":"/key-papers/paper-checkmate-141-ferris-nejm-2016/","year":2016,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Nivolumab lengthened survival compared with standard single-agent chemotherapy in head and neck cancer that had progressed within six months of platinum treatment, the first immunotherapy to improve survival in the disease.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-heracles-lancet-oncol-2016","kind":"paper","name":"HERACLES: trastuzumab and lapatinib in HER2-amplified, KRAS wild-type metastatic colorectal cancer","route":"/key-papers/paper-heracles-lancet-oncol-2016/","year":2016,"journal":"The Lancet Oncology","paperType":"observational","tldr":"This small Italian trial was the first to show that HER2-amplified colorectal cancer responds to dual HER2 blockade, establishing HER2 as a genuine drug target in a disease where it had been ignored.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-ielsg32-matrix-induction-ferreri-lancet-haematol-2016","kind":"paper","name":"IELSG32 first randomisation: the MATRix regimen (methotrexate, cytarabine, thiotepa, rituximab) in primary CNS lymphoma","route":"/key-papers/paper-ielsg32-matrix-induction-ferreri-lancet-haematol-2016/","year":2016,"journal":"The Lancet Haematology","paperType":"rct","tldr":"Adding rituximab and thiotepa to methotrexate and cytarabine doubled the complete remission rate for lymphoma confined to the brain, making the four-drug MATRix regimen the standard induction for patients up to 70.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-keynote-010-lancet-2016","kind":"paper","name":"KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer","route":"/key-papers/paper-keynote-010-lancet-2016/","year":2016,"journal":"The Lancet","paperType":"rct","tldr":"After chemotherapy had failed, pembrolizumab prolonged life compared with docetaxel in lung cancers expressing any PD-L1, with the largest gain in tumours where at least half the cells were positive, and caused fewer severe side effects.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-024-nejm-2016","kind":"paper","name":"KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer","route":"/key-papers/paper-keynote-024-nejm-2016/","year":2016,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In patients whose lung tumours carried PD-L1 on at least half their cells, pembrolizumab alone held the cancer back longer than chemotherapy and caused fewer serious side effects, making immunotherapy the first treatment for this group.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-apt-tolaney-nejm-2015","kind":"paper","name":"APT: adjuvant paclitaxel and trastuzumab for small, node-negative HER2-positive breast cancer","route":"/key-papers/paper-apt-tolaney-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Twelve weeks of paclitaxel with a year of trastuzumab, and no anthracycline, was enough to keep more than 98 percent of women with small node-negative HER2-positive breast cancers free of recurrence at three years.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-checkmate-017-nejm-2015","kind":"paper","name":"CheckMate 017: nivolumab beats docetaxel in squamous lung cancer after chemotherapy","route":"/key-papers/paper-checkmate-017-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"In squamous non-small-cell lung cancer that had progressed after platinum chemotherapy, the PD-1 antibody nivolumab prolonged life compared with docetaxel with far fewer severe side effects, regardless of PD-L1 status.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-checkmate-057-nejm-2015","kind":"paper","name":"CheckMate 057: nivolumab beats docetaxel after chemotherapy in non-squamous lung cancer","route":"/key-papers/paper-checkmate-057-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"After platinum chemotherapy had failed, the PD-1 antibody nivolumab prolonged life compared with docetaxel in non-squamous lung cancer with far fewer severe side effects, and the benefit was largest in tumours expressing PD-L1.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"id":"paper-keynote-001-pembrolizumab-nsclc-nejm-2015","kind":"paper","name":"KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off","route":"/key-papers/paper-keynote-001-pembrolizumab-nsclc-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"translational","tldr":"The large early trial that showed pembrolizumab shrinks about a fifth of advanced lung cancers, with responses that last, and that identified a PD-L1 score of 50% or more as the group most likely to benefit.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015","kind":"paper","name":"KEYNOTE-006 (Robert 2015): pembrolizumab versus ipilimumab in advanced melanoma","route":"/key-papers/paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Head to head, the PD-1 antibody pembrolizumab held melanoma back longer, prolonged life and caused fewer severe side effects than ipilimumab, the CTLA-4 antibody that had been the first immunotherapy to extend survival.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-le-mmr-deficiency-pd1-nejm-2015","kind":"paper","name":"Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ","route":"/key-papers/paper-le-mmr-deficiency-pd1-nejm-2015/","year":2015,"journal":"New England Journal of Medicine","paperType":"translational","tldr":"Pembrolizumab shrank tumours in 40% of colorectal and 71% of other cancers with faulty DNA mismatch repair, but in none with intact repair, tying immunotherapy response to mutation burden.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-rizvi-mutational-landscape-pd1-science-2015","kind":"paper","name":"Rizvi 2015: the mutational landscape determines who responds to PD-1 blockade in lung cancer","route":"/key-papers/paper-rizvi-mutational-landscape-pd1-science-2015/","year":2015,"journal":"Science","paperType":"translational","tldr":"Lung cancers with more mutations, typically those caused by smoking, were more likely to respond to pembrolizumab, the study that established tumour mutational burden as a biomarker for immunotherapy.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-aurelia-jco-2014","kind":"paper","name":"AURELIA: bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer","route":"/key-papers/paper-aurelia-jco-2014/","year":2014,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding bevacizumab to single-agent chemotherapy doubled the time to progression and the response rate in platinum-resistant ovarian cancer, becoming the first regimen to improve outcomes in this hard-to-treat setting.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-aurelia-bevacizumab-platinum-resistant-ovarian-pujade-lauraine-jco-2014","kind":"paper","name":"AURELIA: bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer","route":"/key-papers/paper-aurelia-bevacizumab-platinum-resistant-ovarian-pujade-lauraine-jco-2014/","year":2014,"journal":"Journal of Clinical Oncology","paperType":"rct","tldr":"Adding bevacizumab to single-agent chemotherapy for platinum-resistant ovarian cancer doubled the time to progression and more than doubled the response rate, without a significant gain in survival.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-gog-240-bevacizumab-cervical-nejm-2014","kind":"paper","name":"GOG 240: bevacizumab added to chemotherapy for advanced cervical cancer","route":"/key-papers/paper-gog-240-bevacizumab-cervical-nejm-2014/","year":2014,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the anti-angiogenic antibody bevacizumab to chemotherapy lengthened survival by almost four months in recurrent or metastatic cervical cancer, the first targeted drug to improve survival in a gynaecological cancer.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-rainbow-ramucirumab-paclitaxel-lancet-oncol-2014","kind":"paper","name":"RAINBOW: ramucirumab plus paclitaxel versus placebo plus paclitaxel in previously treated advanced gastric cancer","route":"/key-papers/paper-rainbow-ramucirumab-paclitaxel-lancet-oncol-2014/","year":2014,"journal":"The Lancet Oncology","paperType":"rct","tldr":"Adding the anti-VEGFR2 antibody ramucirumab to weekly paclitaxel lengthened survival by over two months in gastric cancer that had progressed after first-line chemotherapy, establishing the standard second-line regimen.","via":[{"id":"ramucirumab","kind":"drug","name":"Ramucirumab","route":"/drugs/ramucirumab/"}]},{"id":"paper-tumeh-pd1-adaptive-immune-resistance-nature-2014","kind":"paper","name":"Tumeh 2014: PD-1 blockade works by releasing T cells already present at the tumour edge","route":"/key-papers/paper-tumeh-pd1-adaptive-immune-resistance-nature-2014/","year":2014,"journal":"Nature","paperType":"translational","tldr":"Melanomas that responded to pembrolizumab already contained killer T cells pressed up against tumour cells expressing PD-L1, showing that the drug works by releasing an immune attack that is already there rather than creating a new one.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"paper-chen-mellman-cancer-immunity-cycle-immunity-2013","kind":"paper","name":"Chen and Mellman 2013: the cancer-immunity cycle","route":"/key-papers/paper-chen-mellman-cancer-immunity-cycle-immunity-2013/","year":2013,"journal":"Immunity","paperType":"review","tldr":"The seven-step diagram of how the immune system should destroy a cancer, from releasing tumour antigens to killing tumour cells, and the idea that each patient's cancer breaks the cycle at a different step, which tells you which immunotherapies to combine.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-dunleavy-da-epoch-r-pmbcl-nejm-2013","kind":"paper","name":"Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma","route":"/key-papers/paper-dunleavy-da-epoch-r-pmbcl-nejm-2013/","year":2013,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"Infusional dose-adjusted EPOCH with rituximab cured almost every patient with primary mediastinal B-cell lymphoma without any radiotherapy, sparing young patients the heart and breast cancer risks of chest irradiation.","via":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]},{"id":"paper-pardoll-immune-checkpoint-blockade-nrc-2012","kind":"paper","name":"Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy","route":"/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/","year":2012,"journal":"Nature Reviews Cancer","paperType":"review","tldr":"The review that named and organised the field of checkpoint blockade: tumours switch off attacking T cells through brakes such as CTLA-4 and PD-1, and antibodies that release those brakes can produce lasting responses.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-topalian-anti-pd1-nejm-2012","kind":"paper","name":"Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer","route":"/key-papers/paper-topalian-anti-pd1-nejm-2012/","year":2012,"journal":"New England Journal of Medicine","paperType":"translational","tldr":"Nivolumab shrank tumours in roughly a fifth to a quarter of patients with three different advanced cancers, with responses that lasted more than a year and a hint that PD-L1 on the tumour predicted benefit.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-schreiber-cancer-immunoediting-science-2011","kind":"paper","name":"Schreiber, Old and Smyth 2011: cancer immunoediting","route":"/key-papers/paper-schreiber-cancer-immunoediting-science-2011/","year":2011,"journal":"Science","paperType":"review","tldr":"The review that set out the three Es of how the immune system shapes a cancer: elimination of many early tumours, an equilibrium in which growth is held in check, and escape when the tumour evolves ways to evade attack.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-hodi-ipilimumab-melanoma-nejm-2010","kind":"paper","name":"Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma","route":"/key-papers/paper-hodi-ipilimumab-melanoma-nejm-2010/","year":2010,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Blocking the immune brake CTLA-4 was the first treatment ever to prolong life in metastatic melanoma, with about one in five patients alive at two years and a new class of autoimmune side effects.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-toga-trastuzumab-gastric-lancet-2010","kind":"paper","name":"ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer","route":"/key-papers/paper-toga-trastuzumab-gastric-lancet-2010/","year":2010,"journal":"The Lancet","paperType":"rct","tldr":"The trial that brought HER2 testing and trastuzumab to stomach cancer: adding the antibody to chemotherapy prolonged survival in patients whose gastric or junction cancers overexpressed HER2, about a fifth of those screened.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-plotkin-bevacizumab-nf2-nejm-2009","kind":"paper","name":"Hearing improvement after bevacizumab in patients with neurofibromatosis type 2","route":"/key-papers/paper-plotkin-bevacizumab-nf2-nejm-2009/","year":2009,"journal":"New England Journal of Medicine","paperType":"observational","tldr":"In a small series of people with NF2 and progressive vestibular schwannomas, the anti-VEGF antibody bevacizumab shrank the tumours in most and, remarkably, improved hearing in more than half, opening the first drug treatment for these tumours.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-extreme-vermorken-nejm-2008","kind":"paper","name":"EXTREME: platinum-based chemotherapy plus cetuximab in recurrent or metastatic head and neck cancer","route":"/key-papers/paper-extreme-vermorken-nejm-2008/","year":2008,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding cetuximab to platinum and fluorouracil lengthened survival in recurrent or metastatic head and neck cancer from 7.4 to 10.1 months, the first improvement in first-line treatment in decades.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-bonner-cetuximab-radiotherapy-nejm-2006","kind":"paper","name":"Radiotherapy plus cetuximab for locoregionally advanced squamous cell carcinoma of the head and neck","route":"/key-papers/paper-bonner-cetuximab-radiotherapy-nejm-2006/","year":2006,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the EGFR antibody cetuximab to radiotherapy lengthened survival in locally advanced head and neck cancer by about 20 months without increasing the mucosal toxicity of radiotherapy, giving patients unfit for cisplatin an alternative.","via":[{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"}]},{"id":"paper-hurwitz-bevacizumab-crc-nejm-2004","kind":"paper","name":"Hurwitz 2004: bevacizumab with chemotherapy for metastatic colorectal cancer, the first anti-angiogenic drug to extend life","route":"/key-papers/paper-hurwitz-bevacizumab-crc-nejm-2004/","year":2004,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"Adding the VEGF antibody bevacizumab to irinotecan-based chemotherapy prolonged survival in first-line metastatic colorectal cancer, the first time blocking a tumour's blood supply had been shown to help patients.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"}]},{"id":"paper-coussens-werb-inflammation-cancer-nature-2002","kind":"paper","name":"Coussens and Werb 2002: inflammation and cancer","route":"/key-papers/paper-coussens-werb-inflammation-cancer-nature-2002/","year":2002,"journal":"Nature","paperType":"review","tldr":"The review that made the immune cells inside a tumour part of the disease: long-running inflammation, whether from infection, irritation or the tumour's own signals, supplies growth factors, blood vessels and DNA damage that help cancers start and spread.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-iwai-pdl1-tumour-escape-pnas-2002","kind":"paper","name":"Iwai and Honjo: tumours use PD-L1 to escape T cells, and blocking it restores attack","route":"/key-papers/paper-iwai-pdl1-tumour-escape-pnas-2002/","year":2002,"journal":"PNAS","paperType":"basic","tldr":"A decade after Honjo's group cloned PD-1 (1992), this study showed that tumour cells expressing PD-L1 resist killing by cytotoxic T cells in mice, and that anti-PD-L1 antibody or PD-1 deficiency restores tumour rejection, the foundation of PD-1/PD-L1 therapy.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"paper-slamon-trastuzumab-nejm-2001","kind":"paper","name":"Slamon 2001: adding trastuzumab to chemotherapy for HER2-positive metastatic breast cancer","route":"/key-papers/paper-slamon-trastuzumab-nejm-2001/","year":2001,"journal":"New England Journal of Medicine","paperType":"rct","tldr":"The trial that made trastuzumab standard: adding the HER2 antibody to chemotherapy slowed progression and prolonged life in women whose breast cancers overexpressed HER2, at the cost of heart weakening when it was paired with anthracyclines.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"paper-leach-allison-ctla4-blockade-science-1996","kind":"paper","name":"Leach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours","route":"/key-papers/paper-leach-allison-ctla4-blockade-science-1996/","year":1996,"journal":"Science","paperType":"basic","tldr":"Injecting mice with an antibody that blocks the T-cell inhibitory receptor CTLA-4 caused established colon carcinomas and fibrosarcomas to be rejected and protected against re-challenge, the experiment that founded checkpoint immunotherapy.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]}],"eras":[{"roadmap":{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},"era":"2025-2026","title":"The first drug approval that depends on a ctDNA result","status":"current","step":6,"route":"/roadmaps/ctdna-tests/#story-step-5","refs":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}]},{"roadmap":{"id":"devices-roadmap","kind":"roadmap","name":"Devices and physical therapies roadmap: heat and light → electric fields and focused sound → drug-releasing implants","route":"/roadmaps/devices-roadmap/"},"era":"2020-2026","title":"Light-activated drugs and drug-releasing implants","status":"current","step":4,"route":"/roadmaps/devices-roadmap/#story-step-3","refs":[{"id":"cetuximab-sarotalocan","kind":"drug","name":"Cetuximab sarotalocan","route":"/drugs/cetuximab-sarotalocan/"}]},{"roadmap":{"id":"gallbladder-cancer-roadmap","kind":"roadmap","name":"Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials","route":"/roadmaps/gallbladder-cancer-roadmap/"},"era":"2022-2025","title":"Immunotherapy joins chemotherapy","status":"current","step":7,"route":"/roadmaps/gallbladder-cancer-roadmap/#story-step-6","refs":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"roadmap":{"id":"global-access-roadmap","kind":"roadmap","name":"Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation","route":"/roadmaps/global-access-roadmap/"},"era":"2012-2020","title":"Biosimilars and pooled procurement","status":"historic","step":2,"route":"/roadmaps/global-access-roadmap/#story-step-1","refs":[{"id":"trastuzumab-biosimilars","kind":"drug","name":"Trastuzumab biosimilars","route":"/drugs/trastuzumab-biosimilars/"}]},{"roadmap":{"id":"global-access-roadmap","kind":"roadmap","name":"Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation","route":"/roadmaps/global-access-roadmap/"},"era":"2018-2026","title":"Homegrown innovation in India and China","status":"current","step":4,"route":"/roadmaps/global-access-roadmap/#story-step-3","refs":[{"id":"sintilimab","kind":"drug","name":"Sintilimab","route":"/drugs/sintilimab/"},{"id":"camrelizumab","kind":"drug","name":"Camrelizumab","route":"/drugs/camrelizumab/"}]},{"roadmap":{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"},"era":"2011-2018","title":"Checkpoint revolution","status":"historic","step":2,"route":"/roadmaps/immunotherapy-roadmap/#story-step-1","refs":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}]},{"roadmap":{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"},"era":"2018-2024","title":"Earlier lines and combinations","status":"current","step":3,"route":"/roadmaps/immunotherapy-roadmap/#story-step-2","refs":[{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/"}]},{"roadmap":{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"},"era":"1994-2015","title":"Immunotherapy for neuroblastoma, and counting the cost of cure","status":"historic","step":2,"route":"/roadmaps/paediatric-oncology-roadmap/#story-step-1","refs":[{"id":"dinutuximab","kind":"drug","name":"Dinutuximab (ch14.18) / dinutuximab beta","route":"/drugs/dinutuximab/"}]},{"roadmap":{"id":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/"},"era":"2017-2026","title":"Radiation plus drugs: what worked and what did not","status":"current","step":3,"route":"/roadmaps/radiation-roadmap/#story-step-2","refs":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"roadmap":{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"},"era":"1977-2001","title":"The idea of a target","status":"historic","step":1,"route":"/roadmaps/targeted-therapy-roadmap/#story-step-0","refs":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"roadmap":{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"},"era":"2018-2024","title":"Immunotherapy: an assay dispute, then a new standard for early disease","status":"current","step":10,"route":"/roadmaps/tnbc-roadmap/#story-step-9","refs":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]}],"ideas":[{"id":"idea-fund-organ-preservation-programme","kind":"idea","name":"A funded programme of organ-preservation trials to avoid radical surgery","route":"/ideas/idea-fund-organ-preservation-programme/","maturity":"being-tested-at-scale","tldr":"For some cancers, drugs and radiotherapy can now cure without removing the organ, sparing patients a stoma, a lost voice or a removed bladder. A dedicated programme would run the trials to prove where this is safe.","via":[{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-tr1-public-de-escalation-trial-fund","kind":"idea","name":"A public fund for trials that test less treatment","route":"/ideas/idea-tr1-public-de-escalation-trial-fund/","maturity":"being-tested-at-scale","tldr":"No company will pay to find out whether six months of its drug works as well as twelve. A dedicated public fund would pay for those trials, which save patients side effects and health systems money.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-acc-risk-stratified-cardio-oncology-pathway","kind":"idea","name":"A risk-stratified cardio-oncology pathway for everyone receiving heart-toxic cancer therapy","route":"/ideas/idea-acc-risk-stratified-cardio-oncology-pathway/","maturity":"being-tested-at-scale","tldr":"Some chemotherapy and antibody drugs damage the heart. Checking heart function before and during treatment and starting protective drugs early for those at risk could prevent much of that damage.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-post-neoadjuvant-adc","kind":"idea","name":"ADC for residual disease after KEYNOTE-522","route":"/ideas/idea-post-neoadjuvant-adc/","maturity":"being-tested-at-scale","tldr":"Patients whose TNBC survives chemo-immunotherapy before surgery have a high relapse risk. Give them an ADC after surgery.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-reg-biosimilar-no-efficacy-trial","kind":"idea","name":"Approve cancer biosimilars on analytics and pharmacokinetics, no efficacy trials","route":"/ideas/idea-reg-biosimilar-no-efficacy-trial/","maturity":"being-tested-at-scale","tldr":"Copies of biological cancer drugs are still required to run large trials that rarely change the answer. Dropping them would cut years and tens of millions from each biosimilar.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-reg-market-expansion-repricing","kind":"idea","name":"Automatic price cuts when a cancer drug's approved indications and volumes expand","route":"/ideas/idea-reg-market-expansion-repricing/","maturity":"being-tested-at-scale","tldr":"When a cancer drug is approved for more uses, the company sells far more of it but the price stays the same. Japan cuts prices automatically when sales balloon; others should too.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-reg-biosimilar-first-default-switching","kind":"idea","name":"Biosimilar-first defaults and payment parity in every cancer day unit","route":"/ideas/idea-reg-biosimilar-first-default-switching/","maturity":"being-tested-at-scale","tldr":"Cheaper copies of biological cancer drugs exist but are used far less in some countries than others. Making them the default choice saves billions with no loss of benefit.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-gbc-neoadjuvant-for-high-risk-incidental-cancer","kind":"idea","name":"Chemotherapy before the second operation for high-risk incidental gallbladder cancer","route":"/ideas/idea-gbc-neoadjuvant-for-high-risk-incidental-cancer/","maturity":"being-tested-at-scale","tldr":"Gallbladder cancers found by chance often come back within six months of the second operation, usually far from the gallbladder, which suggests the disease was already in the bloodstream. Two randomised trials are testing chemotherapy first; one closed small, the other reports in 2028.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"idea-tnbc-de-escalation-for-exceptional-responders","kind":"idea","name":"Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease","route":"/ideas/idea-tnbc-de-escalation-for-exceptional-responders/","maturity":"being-tested-at-scale","tldr":"Two thirds of women treated on the KEYNOTE-522 regimen have no tumour left at surgery and about 92 percent of them are alive without relapse at five years, yet all receive nine more cycles of pembrolizumab. Trials are now testing whether the best responders can stop early, skip the anthracycline, or in lymphocyte-rich stage I tumours skip chemotherapy altogether.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-acc-home-chemotherapy-older-patients","kind":"idea","name":"Home administration of selected chemotherapy and immunotherapy for older and frail patients","route":"/ideas/idea-acc-home-chemotherapy-older-patients/","maturity":"being-tested-at-scale","tldr":"For frail older patients, the journey to hospital can be the hardest part of treatment. Nurses can safely give some cancer treatments at home, which may help more people complete their course.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-cost-extended-interval-default","kind":"idea","name":"Make six-weekly immunotherapy the default schedule","route":"/ideas/idea-cost-extended-interval-default/","maturity":"being-tested-at-scale","tldr":"Pembrolizumab 400 mg every six weeks is approved and works like 200 mg every three weeks, and it halves the number of clinic visits, infusion chairs and travel days without changing the drug bill.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-cost-biosimilar-default-substitution","kind":"idea","name":"Make the biosimilar the default at the pharmacy for trastuzumab, bevacizumab and rituximab","route":"/ideas/idea-cost-biosimilar-default-substitution/","maturity":"being-tested-at-scale","tldr":"Copies of the big antibody drugs are approved and cheaper, but uptake depends on each prescriber; letting the pharmacy substitute the biosimilar unless the oncologist objects would move most patients within a year.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-biosimilars","kind":"drug","name":"Trastuzumab biosimilars","route":"/drugs/trastuzumab-biosimilars/"}]},{"id":"idea-molecular-class-adjuvant-endometrial","kind":"idea","name":"Molecular-class-directed adjuvant therapy in endometrial cancer","route":"/ideas/idea-molecular-class-adjuvant-endometrial/","maturity":"being-tested-at-scale","tldr":"Give adjuvant treatment by the tumour's molecular class rather than by stage and grade: nothing for POLE-mutated, immunotherapy for MMRd, chemotherapy plus targeted agents for p53-abnormal, hormones for NSMP.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"idea-mrd-guided-stop-myeloma","kind":"idea","name":"MRD-guided treatment-free intervals in myeloma","route":"/ideas/idea-mrd-guided-stop-myeloma/","maturity":"being-tested-at-scale","tldr":"If a patient has had no detectable myeloma for a year or more, stop maintenance and watch, restarting only if disease reappears.","via":[{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"}]},{"id":"idea-organ-preservation-esophageal","kind":"idea","name":"Organ preservation as the default after complete response in oesophageal cancer","route":"/ideas/idea-organ-preservation-esophageal/","maturity":"being-tested-at-scale","tldr":"Oesophagectomy is one of the hardest operations in surgery. If chemoradiation (with or without immunotherapy) has made the tumour disappear, skip it and watch.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-pooled-procurement-adult-essentials","kind":"idea","name":"Pooled international procurement of essential adult cancer medicines","route":"/ideas/idea-reg-pooled-procurement-adult-essentials/","maturity":"being-tested-at-scale","tldr":"Countries buying cancer drugs alone pay more and face shortages. Buying together, as they already do for childhood cancer drugs and vaccines, cuts prices and secures supply.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-tr1-public-dose-reduction-trials-of-approved-drugs","kind":"idea","name":"Publicly funded dose-reduction trials of expensive approved drugs","route":"/ideas/idea-tr1-public-dose-reduction-trials-of-approved-drugs/","maturity":"being-tested-at-scale","tldr":"Some expensive approved cancer drugs probably work as well at lower doses, as reduced-dose abiraterone with food and extended-interval checkpoint inhibitors suggest. Companies will not test this, so payers should fund randomised non-inferiority trials prioritised by spend and pharmacology, and use the results in reimbursement.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-public-deescalation-trials-for-cost","kind":"idea","name":"Publicly funded trials of lower and less frequent doses of expensive cancer drugs","route":"/ideas/idea-reg-public-deescalation-trials-for-cost/","maturity":"being-tested-at-scale","tldr":"Abiraterone at a quarter dose with food matches full-dose exposure, and pembrolizumab and nivolumab can be given at longer intervals, but no manufacturer will fund trials that cut its own revenue. A public 'value trials' fund would run non-inferiority trials of lower doses and longer intervals for the highest-spend cancer drugs, with payers committing to adopt positive results.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-tr1-immunotherapy-stop-trials","kind":"idea","name":"Randomised trials of stopping immunotherapy after one year versus continuing","route":"/ideas/idea-tr1-immunotherapy-stop-trials/","maturity":"being-tested-at-scale","tldr":"Immunotherapy is often given for two years or until it stops working, but responses can last long after stopping. Trials that randomly assign responders to stop or continue would show whether the extra year is needed.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-neoadjuvant-biomarker-engine","kind":"idea","name":"Use pre-surgery immunotherapy windows as the field's biomarker engine","route":"/ideas/idea-bio2-neoadjuvant-biomarker-engine/","maturity":"being-tested-at-scale","tldr":"Giving immunotherapy for a few weeks before surgery produces a tumour sample that shows exactly what the drug did. That is the fastest way to learn who responds.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-gbc-ctdna-residual-disease-guided-adjuvant-trial","kind":"idea","name":"A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection","route":"/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/","maturity":"early-clinical","tldr":"After surgery for bile duct or gallbladder cancer, a blood test for leftover tumour DNA picks out the people whose cancer will return with hazard ratios of 16 to 26 in two recent cohorts. Nobody has yet tested giving those people more than the standard capecitabine.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"}]},{"id":"idea-acc-national-late-effects-registry","kind":"idea","name":"A national late-effects registry linking treatment exposures to outcomes decades later","route":"/ideas/idea-acc-national-late-effects-registry/","maturity":"early-clinical","tldr":"We know surprisingly little about what happens to cancer survivors twenty years on. Linking their treatment records to later health records would show which treatments cause which problems and who needs watching.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-rt-io-platform","kind":"idea","name":"A neutral platform trial for radiotherapy plus immunotherapy combinations","route":"/ideas/idea-fund-rt-io-platform/","maturity":"early-clinical","tldr":"Radiotherapy may make immunotherapy work better, but the trials to test this are scattered and often small. One shared platform, run by radiotherapy groups with drugs supplied by several companies, would settle it faster.","via":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-tmb-calibration-standard","kind":"idea","name":"A single calibrated tumour mutational burden across all sequencing panels","route":"/ideas/idea-tr2-tmb-calibration-standard/","maturity":"early-clinical","tldr":"Tumour mutational burden decides who gets immunotherapy in some settings, but every sequencing panel calculates it differently. A shared calibration would make the number mean the same thing everywhere.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-adc-for-mesothelioma","kind":"idea","name":"Antibody-drug conjugates for mesothelioma: why they have failed so far and how they could work","route":"/ideas/idea-adc-for-mesothelioma/","maturity":"early-clinical","tldr":"Nearly every mesothelioma carries the surface protein mesothelin, yet the one antibody-drug conjugate tried in a randomised trial did no better than chemotherapy. The idea is to fix the three reasons it failed rather than abandon the approach.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-biomarker-quadruplet-gastric","kind":"idea","name":"Biomarker-directed first-line quadruplets in gastric cancer","route":"/ideas/idea-biomarker-quadruplet-gastric/","maturity":"early-clinical","tldr":"Stomach cancer now has three add-on biomarkers (HER2, PD-L1, Claudin 18.2) that often overlap. Test whether combining two add-ons beats picking one.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"tislelizumab","kind":"drug","name":"Tislelizumab","route":"/drugs/tislelizumab/"},{"id":"zolbetuximab","kind":"drug","name":"Zolbetuximab","route":"/drugs/zolbetuximab/"}]},{"id":"idea-moon-cardioprotection-by-default","kind":"idea","name":"Biomarker-guided cardioprotection for everyone on cardiotoxic cancer therapy","route":"/ideas/idea-moon-cardioprotection-by-default/","maturity":"early-clinical","tldr":"Anthracyclines, HER2 drugs and some newer agents can damage the heart. Monitor with blood tests and scans and start cheap heart-protective drugs early in those at risk.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-adjuvant-selection-rcc","kind":"idea","name":"Biomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)","route":"/ideas/idea-adjuvant-selection-rcc/","maturity":"early-clinical","tldr":"Adjuvant immunotherapy after kidney cancer surgery is given to everyone at high pathological risk although most would never relapse, so a year of toxicity is spread across the whole group to help a minority. A biomarker such as CAIX PET or kidney-specific tumour DNA could pick out the few who need it.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-bladder-preservation-mibc","kind":"idea","name":"Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response","route":"/ideas/idea-bladder-preservation-mibc/","maturity":"early-clinical","tldr":"If the ADC-immunotherapy combination erases the tumour in more than half of patients before surgery, some may not need their bladder removed at all.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-atc-triplet-io","kind":"idea","name":"BRAF/MEK plus PD-1 blockade as standard for BRAF-mutant anaplastic thyroid cancer","route":"/ideas/idea-atc-triplet-io/","maturity":"early-clinical","tldr":"Add immunotherapy to the two targeted pills in the most aggressive thyroid cancer, because the combination has produced multi-year survivors in early series.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-tdxd-first-then-nothing","kind":"idea","name":"Can T-DXd alone cure early HER2-positive disease?","route":"/ideas/idea-tdxd-first-then-nothing/","maturity":"early-clinical","tldr":"If Enhertu produces complete responses in two-thirds of patients before surgery, a trial should test whether some need no chemotherapy, antibodies, or even radiation afterwards.","via":[{"id":"pertuzumab","kind":"drug","name":"Pertuzumab","route":"/drugs/pertuzumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-cd8-pet-io","kind":"idea","name":"CD8 PET to stop or switch immunotherapy early","route":"/ideas/idea-cd8-pet-io/","maturity":"early-clinical","tldr":"Scan for T cells inside the tumour a few weeks after starting immunotherapy. If they have not arrived, change course.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-chemo-free-hodgkin","kind":"idea","name":"Chemotherapy-free Hodgkin lymphoma: brentuximab + PD-1 in early stage","route":"/ideas/idea-chemo-free-hodgkin/","maturity":"early-clinical","tldr":"For a cancer already cured in 90% of young people, the goal is curing without the chemotherapy and radiation that cause heart disease and second cancers decades later.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-cxcr2-neutrophil-blockade","kind":"idea","name":"Clear the suppressive neutrophils out of pancreatic tumours first","route":"/ideas/idea-bio2-cxcr2-neutrophil-blockade/","maturity":"early-clinical","tldr":"Pancreatic tumours are packed with a type of white blood cell that shuts down the immune attack. Blocking the signal that recruits them may open the tumour to immunotherapy.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-gdf15-plus-exercise","kind":"idea","name":"Combine the new anti-wasting antibody with exercise and protein","route":"/ideas/idea-bio2-gdf15-plus-exercise/","maturity":"early-clinical","tldr":"A new antibody blocks the hormone that makes people with cancer lose appetite and weight. Weight regained as muscle, not fat, needs exercise and protein alongside it.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-tr1-low-dose-immunotherapy-for-lmic","kind":"idea","name":"Confirm ultra-low-dose immunotherapy so it can be afforded where most patients live","route":"/ideas/idea-tr1-low-dose-immunotherapy-for-lmic/","maturity":"early-clinical","tldr":"A single-centre trial at Tata Memorial found that adding nivolumab at about a twentieth of the usual dose to chemotherapy improved outcomes in head and neck cancer. Confirmatory trials against standard-dose immunotherapy are needed before low-dose labels could make immunotherapy affordable for millions.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tnbc-ctdna-guided-adjuvant-decisions","kind":"idea","name":"ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative","route":"/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/","maturity":"early-clinical","tldr":"After pre-surgery chemotherapy leaves tumour behind, a blood test for tumour DNA triples the risk of distant relapse when positive. The one trial that acted on it found the DNA usually appeared too late. A trial that tests at surgery with a tumour-informed assay, escalates positives to an antibody-drug conjugate and observes negatives has not been run.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-ctdna-guided-adjuvant-melanoma","kind":"idea","name":"ctDNA-guided adjuvant therapy in stage II-III melanoma","route":"/ideas/idea-ctdna-guided-adjuvant-melanoma/","maturity":"early-clinical","tldr":"Most stage II patients never relapse, yet all are offered a year of immunotherapy. Use a blood test to treat only those with detectable residual disease.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr1-extended-interval-checkpoint-dosing","kind":"idea","name":"Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable","route":"/ideas/idea-tr1-extended-interval-checkpoint-dosing/","maturity":"early-clinical","tldr":"Immunotherapy antibodies stay active in the body for weeks, yet are often given every two or three weeks. After a few months, spacing doses out to every two or three months might work as well, with fewer hospital visits and much lower cost.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-combo-dose-matrix","kind":"idea","name":"Find the lowest effective doses of both drugs in a combination, not the highest tolerated","route":"/ideas/idea-tr2-combo-dose-matrix/","maturity":"early-clinical","tldr":"Combination trials usually keep one drug at full dose and push the other as high as patients can bear. Testing a grid of dose pairs would find combinations that work at lower, safer doses.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-cost-shorter-course-trials","kind":"idea","name":"Fund trials that test shorter courses of the most expensive adjuvant drugs","route":"/ideas/idea-cost-shorter-course-trials/","maturity":"early-clinical","tldr":"The PERSEPHONE trial showed six months of trastuzumab after surgery is as good as twelve, halving the drug cost; no company will run such trials, so public funders and charities must.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-chronotherapy-immunotherapy","kind":"idea","name":"Give immunotherapy in the morning","route":"/ideas/idea-chronotherapy-immunotherapy/","maturity":"early-clinical","tldr":"Several studies found patients infused with checkpoint inhibitors earlier in the day lived longer. If a randomised trial confirms it, it is a free improvement available everywhere tomorrow.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-cost-subcutaneous-community","kind":"idea","name":"Give subcutaneous immunotherapy in community clinics and at home","route":"/ideas/idea-cost-subcutaneous-community/","maturity":"early-clinical","tldr":"Under-the-skin versions of atezolizumab, nivolumab and pembrolizumab take minutes rather than an hour and need no infusion chair, so they can be given by a nurse near home, cutting facility fees and travel.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tnbc-pd-l1-assay-harmonisation","kind":"idea","name":"Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance","route":"/ideas/idea-tnbc-pd-l1-assay-harmonisation/","maturity":"early-clinical","tldr":"Three PD-L1 tests run on the same tumours called 46, 75 and 73 percent of them positive and agreed only 69 percent of the time. With atezolizumab withdrawn, pembrolizumab's test (22C3, combined positive score of 10) is the only one that matters, yet laboratories still run whichever kit they have. One assay, one score and a proficiency scheme would end answers that vary by postcode.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-her2-adc-serous-endometrial","kind":"idea","name":"HER2 ADCs as standard for HER2-positive serous endometrial cancer","route":"/ideas/idea-her2-adc-serous-endometrial/","maturity":"early-clinical","tldr":"Serous endometrial cancers often overproduce HER2. Enhertu already works in them; testing HER2 in every p53-abnormal tumour and using the ADC earlier could change outcomes for the worst subtype.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-tr1-home-infusion-trial-drugs","kind":"idea","name":"Home infusion and local blood draws for trial drugs after the first cycles","route":"/ideas/idea-tr1-home-infusion-trial-drugs/","maturity":"early-clinical","tldr":"Once a patient has safely had the first few doses of a trial drug at the hospital, later doses could be given at home or a local clinic, with blood tests done nearby, so distance no longer decides who can join.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-hpv-ctdna-cervical","kind":"idea","name":"HPV circulating tumour DNA to guide cervical cancer therapy","route":"/ideas/idea-hpv-ctdna-cervical/","maturity":"early-clinical","tldr":"Because cervical tumours carry viral DNA that normal cells do not, a blood test for HPV DNA is a near-perfect tumour marker for tracking response and relapse.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-hcc-io-before-transplant","kind":"idea","name":"Immunotherapy downstaging to transplant with a safe washout","route":"/ideas/idea-hcc-io-before-transplant/","maturity":"early-clinical","tldr":"Use immunotherapy to shrink liver cancer enough for a transplant, and find the safe gap between the last dose and surgery so the new liver is not rejected.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-implantable-microdevice-screen","kind":"idea","name":"Implant a tiny device that tests twenty drugs inside the patient's own tumour","route":"/ideas/idea-bio2-implantable-microdevice-screen/","maturity":"early-clinical","tldr":"A rice-grain-sized implant releases microdoses of up to 20 drugs into separate spots of a tumour for one to three days, then is removed so pathologists can see which drug worked in that person's own tumour. First-in-human studies have been done in breast, sarcoma and brain tumours.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-immunotherapy-mss-crc","kind":"idea","name":"Making microsatellite-stable colorectal cancer immunotherapy-responsive","route":"/ideas/idea-immunotherapy-mss-crc/","maturity":"early-clinical","tldr":"Ninety-five percent of bowel cancers ignore immunotherapy. Combinations that heat the tumour up (targeted drugs, radiation, new checkpoints) are the main hope.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-histotripsy-immune-priming","kind":"idea","name":"Mechanically pulverise one tumour with ultrasound to wake the immune system","route":"/ideas/idea-bio2-histotripsy-immune-priming/","maturity":"early-clinical","tldr":"Focused ultrasound can break a tumour apart without heat or cuts, leaving debris the immune system can learn from. Doing that to one tumour may help treat the rest.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-neoadjuvant-adc-io","kind":"idea","name":"Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC","route":"/ideas/idea-neoadjuvant-adc-io/","maturity":"early-clinical","tldr":"Replace the toughest part of pre-surgery chemotherapy with an ADC plus immunotherapy, aiming for the same cure rate with less harm.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-neoadjuvant-io-glioblastoma","kind":"idea","name":"Neoadjuvant immunotherapy with surgical window for glioblastoma","route":"/ideas/idea-neoadjuvant-io-glioblastoma/","maturity":"early-clinical","tldr":"Give immunotherapy before surgery rather than after, so the tumour is still present to teach the immune system, then look inside it to learn what happened.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-contribution-of-components-mandate","kind":"idea","name":"No accelerated approval for a combination without proof each part contributes","route":"/ideas/idea-tr2-contribution-of-components-mandate/","maturity":"early-clinical","tldr":"Regulators should refuse to approve a two-drug combination unless there is evidence that both drugs are doing something, so patients are not exposed to useless extra toxicity and cost.","via":[{"id":"epacadostat","kind":"drug","name":"Epacadostat","route":"/drugs/epacadostat/"},{"id":"tiragolumab","kind":"drug","name":"Tiragolumab","route":"/drugs/tiragolumab/"}]},{"id":"idea-bio2-oncolytic-regulated-il12","kind":"idea","name":"Oncolytic viruses that make interleukin-12 only inside the tumour","route":"/ideas/idea-bio2-oncolytic-regulated-il12/","maturity":"early-clinical","tldr":"Interleukin-12 is an immune-stimulating cytokine that caused severe toxicity when injected into the bloodstream in the 1990s and was abandoned. An oncolytic herpes or adenovirus carrying the interleukin-12 gene under a drug-inducible promoter makes it only inside the tumour, keeping exposure local; trials include recurrent glioblastoma.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-pdl1-digital-calibration","kind":"idea","name":"One digital PD-L1 scale that maps across all the competing assays","route":"/ideas/idea-tr2-pdl1-digital-calibration/","maturity":"early-clinical","tldr":"There are several different PD-L1 tests, each tied to a different drug, and they disagree. A single digitally calibrated scale would let any lab's result be translated into any drug's cut-off.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-indication-specific-pricing","kind":"idea","name":"Pay a different price for the same cancer drug depending on the indication","route":"/ideas/idea-reg-indication-specific-pricing/","maturity":"early-clinical","tldr":"One immunotherapy may add years of life in one cancer and weeks in another, yet costs the same. Prices should track the benefit in each use.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-fund-payer-funded-pragmatic-trials","kind":"idea","name":"Payers fund trials of cheaper, shorter or lower-dose versions of expensive treatments","route":"/ideas/idea-fund-payer-funded-pragmatic-trials/","maturity":"early-clinical","tldr":"Health insurers and national health systems have every reason to find out whether half the dose or half the duration of a costly drug works as well. They would fund those trials directly and keep the savings.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-photoimmunotherapy-plus-pd1","kind":"idea","name":"Photoimmunotherapy as an in situ vaccine with PD-1 blockade","route":"/ideas/idea-photoimmunotherapy-plus-pd1/","maturity":"early-clinical","tldr":"Bursting tumour cells with light releases their contents to the immune system; adding immunotherapy might turn a local treatment into a body-wide one.","via":[{"id":"cetuximab-sarotalocan","kind":"drug","name":"Cetuximab sarotalocan","route":"/drugs/cetuximab-sarotalocan/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-moon-pooled-procurement-licensing-pool","kind":"idea","name":"Pooled procurement and voluntary licensing for essential cancer medicines in low-income countries","route":"/ideas/idea-moon-pooled-procurement-licensing-pool/","maturity":"early-clinical","tldr":"Buy essential cancer drugs for many countries at once and license newer ones to generic makers, as was done for HIV, so prices fall to what those health systems can pay.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-cost-indication-based-pricing","kind":"idea","name":"Price a cancer drug by how well it works in each cancer","route":"/ideas/idea-cost-indication-based-pricing/","maturity":"early-clinical","tldr":"A drug that adds a year of life in one cancer and six weeks in another sells at the same price for both; indication-specific prices would pay for the benefit actually delivered.","via":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-bio2-antibiotic-stewardship-io","kind":"idea","name":"Protect the gut flora of patients about to start immunotherapy","route":"/ideas/idea-bio2-antibiotic-stewardship-io/","maturity":"early-clinical","tldr":"Antibiotics given in the weeks before immunotherapy are linked to much worse results. A simple stewardship rule could preserve benefit at no cost.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-translational-institutes-gmp","kind":"idea","name":"Regional translational institutes with academic GMP suites and IND teams","route":"/ideas/idea-fund-translational-institutes-gmp/","maturity":"early-clinical","tldr":"Build a handful of publicly-funded centres where academic discoveries can be manufactured to clinical grade and written up for regulators, so good ideas do not die for lack of a factory and a filing.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-bio2-trem2-myeloid-reprogramming","kind":"idea","name":"Reprogramme suppressive macrophages instead of trying to delete them","route":"/ideas/idea-bio2-trem2-myeloid-reprogramming/","maturity":"early-clinical","tldr":"Tumours fill with immune cells that protect them. Earlier drugs tried to remove those cells and failed. Newer ones aim to switch them to the attacking side.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-weight-based-io-dosing-label","kind":"idea","name":"Restore weight-based dosing and vial sharing for immunotherapy in the label","route":"/ideas/idea-reg-weight-based-io-dosing-label/","maturity":"early-clinical","tldr":"Immunotherapy is given as one flat dose regardless of body size, which means smaller patients get more than they need. Dosing by weight would save a fifth of the drug at no cost to patients.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr1-model-based-dose-finding-with-late-toxicity","kind":"idea","name":"Retire the 3+3: model-based dose finding that counts late and chronic side effects","route":"/ideas/idea-tr1-model-based-dose-finding-with-late-toxicity/","maturity":"early-clinical","tldr":"The traditional way of finding a dose looks only at severe side effects in the first month. Modern statistical designs can use all patients' data and count the grumbling, long-lasting problems that make people quit months later.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-io-subscription-national","kind":"idea","name":"Subscription pricing for checkpoint inhibitors: fixed national fee, unlimited use","route":"/ideas/idea-reg-io-subscription-national/","maturity":"early-clinical","tldr":"Instead of paying per dose, a country would pay a fixed annual fee and treat every eligible patient with immunotherapy. This has worked for hepatitis C drugs and antibiotics.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-fmt-plus-checkpoint-phase3","kind":"idea","name":"Take faecal transplant plus immunotherapy to a definitive trial","route":"/ideas/idea-bio2-fmt-plus-checkpoint-phase3/","maturity":"early-clinical","tldr":"Transferring gut bacteria from patients who responded to immunotherapy has helped some patients who had stopped responding. It is time for a proper large trial.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-fibre-diet-io-trial","kind":"idea","name":"Test a high-fibre diet as an immunotherapy adjunct","route":"/ideas/idea-bio2-fibre-diet-io-trial/","maturity":"early-clinical","tldr":"People who eat more fibre appear to respond better to immunotherapy, while some probiotic supplements may do the opposite. A proper trial would settle it.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr1-weight-based-vs-flat-dosing-trials","kind":"idea","name":"Test flat versus weight-based dosing of antibodies, and use dose banding to cut waste","route":"/ideas/idea-tr1-weight-based-vs-flat-dosing-trials/","maturity":"early-clinical","tldr":"Monoclonal antibodies and ADCs have moved from weight-based to flat dosing on modelling alone, which is convenient but gives lighter patients relatively more drug. Randomised or pharmacokinetic comparisons, plus rounding doses to vial sizes where exposure is equivalent, could keep effectiveness while cutting cost and waste.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-cost-low-dose-immunotherapy-trials","kind":"idea","name":"Test one-tenth-dose immunotherapy where the full dose is unaffordable","route":"/ideas/idea-cost-low-dose-immunotherapy-trials/","maturity":"early-clinical","tldr":"A randomised trial at Tata Memorial added nivolumab at 20 mg every three weeks, about one-twelfth of the standard dose, to cheap metronomic chemotherapy for head and neck cancer patients who could not afford full-dose immunotherapy, and they lived longer. Checkpoint inhibitors saturate their target far below approved doses, so publicly funded trials should test low doses in common cancers.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-steroid-sparing-irae","kind":"idea","name":"Treat immunotherapy side-effects without wiping out the response","route":"/ideas/idea-bio2-steroid-sparing-irae/","maturity":"early-clinical","tldr":"Immune side-effects are usually treated with high-dose steroids, which may also switch off the anti-cancer response. Targeted alternatives may control the side-effect and keep the benefit.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-intracavitary-immunotherapy","kind":"idea","name":"Treat the body cavity, not the bloodstream, for surface spread","route":"/ideas/idea-bio2-intracavitary-immunotherapy/","maturity":"early-clinical","tldr":"Intracavitary immunotherapy targets cancer that coats the lining of the abdomen or chest, which drugs given by drip barely reach. Delivering it straight into the cavity gives far higher local doses.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-lymph-node-immune-priming","kind":"idea","name":"Treat the draining lymph node before removing it","route":"/ideas/idea-bio2-lymph-node-immune-priming/","maturity":"early-clinical","tldr":"The first lymph node cancer reaches is also where the immune system learns to fight it. Injecting immunotherapy into that node before surgery, instead of removing it blindly, may work better.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-in-situ-vaccination-solid","kind":"idea","name":"Turn one tumour into a vaccine to treat all the others","route":"/ideas/idea-bio2-in-situ-vaccination-solid/","maturity":"early-clinical","tldr":"Injecting immune-activating agents into a single tumour, plus a small dose of radiation, can teach the immune system to attack tumours elsewhere in the body.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-epigenetic-priming-cold-tumours","kind":"idea","name":"Unmask hidden antigens with a short epigenetic course before immunotherapy","route":"/ideas/idea-bio2-epigenetic-priming-cold-tumours/","maturity":"early-clinical","tldr":"Low doses of drugs that change how DNA is packaged can make cancer cells display more of what marks them as abnormal, potentially waking up immunotherapy in cold tumours.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-ctdna-six-week-io-switch","kind":"idea","name":"Use a blood test at six weeks to decide whether to keep going","route":"/ideas/idea-bio2-ctdna-six-week-io-switch/","maturity":"early-clinical","tldr":"Scans at three months often cannot tell whether immunotherapy is working. A blood test at six weeks may give a clearer, earlier answer.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-hypoxia-guided-adenosine","kind":"idea","name":"Use a hypoxia scan to pick patients for adenosine-pathway drugs","route":"/ideas/idea-bio2-hypoxia-guided-adenosine/","maturity":"early-clinical","tldr":"Tumours starved of oxygen produce a chemical that switches immune cells off. A scan can show which tumours are starved, and those are the ones to treat with blockers.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-vascular-normalisation-window","kind":"idea","name":"Use imaging to find the window when tumour blood vessels are working properly","route":"/ideas/idea-bio2-vascular-normalisation-window/","maturity":"early-clinical","tldr":"Low doses of anti-blood-vessel drugs briefly make tumour vessels work better, which helps immune cells and other drugs get in. Scans can find that window for each patient.","via":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-antagonism-surveillance","kind":"idea","name":"Watch routine care for drug combinations that quietly make cancer treatment worse","route":"/ideas/idea-tr2-antagonism-surveillance/","maturity":"early-clinical","tldr":"Some everyday medicines, such as antibiotics or steroids, seem to blunt immunotherapy. Automatically scanning health records for such harmful pairs would catch them years earlier.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-tcr-repertoire-early-readout","kind":"idea","name":"Watch the immune system's response in the blood three weeks in","route":"/ideas/idea-bio2-tcr-repertoire-early-readout/","maturity":"early-clinical","tldr":"When immunotherapy works, specific immune cell families multiply in the blood within weeks. Tracking that could tell patients early whether to continue.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-immune-exclusion-drivers","kind":"idea","name":"What actually holds T cells at the tumour border?","route":"/ideas/idea-immune-exclusion-drivers/","maturity":"early-clinical","tldr":"In immune-excluded tumours T cells reach the border but cannot get in, held back by fibroblasts, matrix, abnormal vessels, CXCL12 gradients or myeloid cells, and TGF-β drugs on their own have failed. If single-cell and spatial profiling can show which stromal programme dominates in each tumour, matching the drug (TGF-β, FAP, CXCR4 or VEGF) to it could let immunotherapy work.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-acc-biosimilar-prequalification-pool","kind":"idea","name":"WHO prequalification plus pooled demand to push biosimilar prices below 10% of the originator","route":"/ideas/idea-acc-biosimilar-prequalification-pool/","maturity":"early-clinical","tldr":"Biosimilars of trastuzumab, rituximab and bevacizumab have existed for years, but poorer countries cannot assess biologics themselves and place small fragmented orders. Extending WHO prequalification, begun with trastuzumab in 2019, to every oncology biosimilar and pooling procurement would give buyers assurance and makers volume, aiming below a tenth of originator prices.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-bio2-tumour-anchored-tgfbeta-trap","kind":"idea","name":"Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere","route":"/ideas/idea-bio2-tumour-anchored-tgfbeta-trap/","maturity":"preclinical-evidence","tldr":"TGF-beta is a signal that keeps immune cells out of tumours, but blocking it throughout the body caused bleeding and heart toxicity and sank bintrafusp alfa. Tethering the blocker to tumour stroma with a FAP anchor, a collagen-binding domain or a protease-activated mask could give the benefit without the harm.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-myeloid-engager-bispecific","kind":"idea","name":"Bispecific antibodies that engage macrophages instead of T cells","route":"/ideas/idea-bio2-myeloid-engager-bispecific/","maturity":"preclinical-evidence","tldr":"Drugs that grab T cells and drag them onto tumours work well in blood cancers. The same trick aimed at tumour-eating cells might work where T cells are absent.","via":[{"id":"magrolimab","kind":"drug","name":"Magrolimab","route":"/drugs/magrolimab/"}]},{"id":"idea-bio2-complement-c5ar-blockade","kind":"idea","name":"Block the complement signal that recruits tumour-protecting cells","route":"/ideas/idea-bio2-complement-c5ar-blockade/","maturity":"preclinical-evidence","tldr":"An old part of the immune system called complement can be hijacked by tumours to summon protective cells. Drugs that block it already exist for other diseases.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-antigen-presentation-triage","kind":"idea","name":"Check whether a tumour can still show itself to the immune system","route":"/ideas/idea-bio2-antigen-presentation-triage/","maturity":"preclinical-evidence","tldr":"Some tumours have broken the machinery that displays their identity to immune cells. Those patients cannot benefit from most immunotherapy and should be routed elsewhere.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-lactate-acid-axis","kind":"idea","name":"De-acidify the tumour so T cells can work in it","route":"/ideas/idea-bio2-lactate-acid-axis/","maturity":"preclinical-evidence","tldr":"Tumours are acidic, and immune cells stop working in acid. Neutralising that acid, or blocking the pumps that create it, might let immunotherapy work.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-evolutionary-double-bind","kind":"idea","name":"Design drug pairs where resisting one makes you vulnerable to the other","route":"/ideas/idea-bio1-evolutionary-double-bind/","maturity":"preclinical-evidence","tldr":"Choose two treatments so that whatever the tumour does to escape the first, it becomes easier to kill with the second. The immune system is a good candidate partner.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-lytac-surface-degraders","kind":"idea","name":"Drag cancer's surface and secreted proteins to the cell's recycling bin","route":"/ideas/idea-bio1-lytac-surface-degraders/","maturity":"preclinical-evidence","tldr":"Some cancer proteins sit on the cell surface or float outside cells, where protein-destroying drugs cannot reach. A different trick can drag them inside to be broken down.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-bio2-tertiary-lymphoid-induction","kind":"idea","name":"Grow immune command posts inside tumours","route":"/ideas/idea-bio2-tertiary-lymphoid-induction/","maturity":"preclinical-evidence","tldr":"Tumours that contain small immune structures resembling lymph nodes respond far better to immunotherapy. Inducing those structures on purpose could make cold tumours responsive.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-immune-matched-humanised-mice","kind":"idea","name":"Humanised mice with an immune system matched to the tumour donor","route":"/ideas/idea-bio1-immune-matched-humanised-mice/","maturity":"preclinical-evidence","tldr":"Most cancer drugs are tested in mice with no immune system, then given to people who have one. Mice carrying the same patient's immune cells and tumour would be a fairer test.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-moon-cold-to-hot-programme","kind":"idea","name":"Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours","route":"/ideas/idea-moon-cold-to-hot-programme/","maturity":"preclinical-evidence","tldr":"Immunotherapy works in tumours that immune cells can enter and ignores those that shut them out. Systematically test ways to open up the shut-out tumours, measured with spatial maps.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-radiotherapy-sting-fractionation","kind":"idea","name":"Pick the radiation dose that switches the immune alarm on, not off","route":"/ideas/idea-bio2-radiotherapy-sting-fractionation/","maturity":"preclinical-evidence","tldr":"Radiation can alert the immune system through the cGAS-STING pathway, but single doses above roughly 12 to 18 Gy switch on the enzyme TREX1, which destroys the alarm signal. Choosing fractionated schedules around 8 Gy times three for immune priming may add benefit at no extra cost.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-moon-irae-prediction-and-prevention","kind":"idea","name":"Predict immune side-effects before they happen and pre-empt them","route":"/ideas/idea-moon-irae-prediction-and-prevention/","maturity":"preclinical-evidence","tldr":"Immunotherapy can trigger dangerous attacks on the gut, lungs or heart. Use blood, gut bacteria and genetic markers to spot who is at risk and act early.","via":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-reg-antihistamine-plus-io-trial","kind":"idea","name":"Randomise a cheap antihistamine alongside immunotherapy","route":"/ideas/idea-reg-antihistamine-plus-io-trial/","maturity":"preclinical-evidence","tldr":"Patients who happened to take common allergy pills during immunotherapy seemed to live longer in a large records study. A simple randomised trial would show whether the pills really help.","via":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-aged-comorbid-models","kind":"idea","name":"Test cancer drugs in old and unhealthy animals, not just young fit ones","route":"/ideas/idea-bio1-aged-comorbid-models/","maturity":"preclinical-evidence","tldr":"Most cancer patients are older and have other illnesses, but nearly all animal experiments use young healthy mice. Results may not transfer.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio1-immunopeptidome-timing","kind":"idea","name":"Time immunotherapy to the moment targeted drugs make tumours visible","route":"/ideas/idea-bio1-immunopeptidome-timing/","maturity":"preclinical-evidence","tldr":"Targeted drugs briefly make cancer cells easier for the immune system to spot. Giving immunotherapy exactly in that window, rather than at the same time, may work better.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-bio2-trained-immunity-priming","kind":"idea","name":"Train the bone marrow to make better anti-tumour immune cells","route":"/ideas/idea-bio2-trained-immunity-priming/","maturity":"preclinical-evidence","tldr":"Certain vaccines and fungal sugars reprogramme the bone marrow so it produces more aggressive immune cells for months. That could be used before immunotherapy.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-abbreviated-pathway-me-too-biologics","kind":"idea","name":"An abbreviated approval path for follow-on antibodies within a validated class","route":"/ideas/idea-fund-abbreviated-pathway-me-too-biologics/","maturity":"speculative","tldr":"Once a class of antibody such as PD-1 blockers is proven, later copies could be approved on smaller trials showing equivalence, forcing price competition and freeing patients and money for genuinely new drugs.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]},{"id":"idea-reg-pd1-biosimilar-advance-commitment","kind":"idea","name":"An advance market commitment for PD-1 biosimilars for lower-income countries","route":"/ideas/idea-reg-pd1-biosimilar-advance-commitment/","maturity":"speculative","tldr":"Immunotherapy patents start expiring around 2028. Guaranteeing in advance to buy cheap copies for poorer countries would make sure manufacturers build the capacity.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-shelved-asset-escrow","kind":"idea","name":"Automatic offer of shelved cancer assets to non-profits after two years","route":"/ideas/idea-fund-shelved-asset-escrow/","maturity":"speculative","tldr":"When a company stops developing a cancer drug for business rather than safety reasons and leaves it idle for two years, it would be obliged to offer the rights, data package and remaining drug supply to qualified non-profit or academic developers on pre-set terms, keeping the right to resume. This turns the stalled-asset registry's listing into a duty.","via":[{"id":"magrolimab","kind":"drug","name":"Magrolimab","route":"/drugs/magrolimab/"},{"id":"tiragolumab","kind":"drug","name":"Tiragolumab","route":"/drugs/tiragolumab/"}]},{"id":"idea-nl-diet-covariates-io-trials","kind":"idea","name":"Capture diet, fibre and antibiotic exposure in every immunotherapy pivotal trial","route":"/ideas/idea-nl-diet-covariates-io-trials/","maturity":"speculative","tldr":"Gut bacteria appear to influence whether immunotherapy works, and diet and antibiotics shape gut bacteria. Yet almost no drug trial records what patients ate or which antibiotics they took. Recording it would cost almost nothing.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-fund-duration-trial-exclusivity","kind":"idea","name":"Extra exclusivity for sponsors who run treatment-duration and de-escalation trials","route":"/ideas/idea-fund-duration-trial-exclusivity/","maturity":"speculative","tldr":"Companies lose money when they prove a shorter course works, so they never test it. Give them a modest reward, such as extra months of exclusivity, when they do.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-tr1-factorial-dose-finding-for-combinations","kind":"idea","name":"Factorial dose finding for drug combinations instead of full dose of everything","route":"/ideas/idea-tr1-factorial-dose-finding-for-combinations/","maturity":"speculative","tldr":"When two cancer drugs are combined, each is usually given at its full single-agent dose, which often proves too toxic. Testing a grid of dose pairs would find combinations that work with tolerable side effects.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-tr2-termination-reports","kind":"idea","name":"Public post-mortem reports when a cancer drug programme is stopped","route":"/ideas/idea-tr2-termination-reports/","maturity":"speculative","tldr":"When an aeroplane crashes, an independent report explains why so it does not happen again. When a cancer drug programme is abandoned, nothing is written. Change that.","via":[{"id":"epacadostat","kind":"drug","name":"Epacadostat","route":"/drugs/epacadostat/"},{"id":"magrolimab","kind":"drug","name":"Magrolimab","route":"/drugs/magrolimab/"}]},{"id":"idea-tr1-pk-informed-organ-thresholds","kind":"idea","name":"Replace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholds","route":"/ideas/idea-tr1-pk-informed-organ-thresholds/","maturity":"speculative","tldr":"Most trials copy the same kidney and liver cut-offs, such as creatinine clearance above 60, regardless of how the drug is cleared. Setting each threshold from the drug's own clearance route and organ-impairment pharmacokinetic studies would let patients with mild organ impairment join safely instead of being excluded.","via":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}]},{"id":"idea-fund-head-to-head-mandate","kind":"idea","name":"Require head-to-head trials against the best in class for later entrants","route":"/ideas/idea-fund-head-to-head-mandate/","maturity":"speculative","tldr":"Once two drugs of a kind exist, a third should have to prove itself against the best of them, not against an outdated comparison, so patients and payers learn which is actually better.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-fund-benefit-indexed-exclusivity","kind":"idea","name":"Shorter exclusivity for later-in-class drugs without added benefit","route":"/ideas/idea-fund-benefit-indexed-exclusivity/","maturity":"speculative","tldr":"The fifth PD-1 antibody that is no better than the first should not get the same market protection as the first. Exclusivity would shrink for copies that add nothing.","via":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}]},{"id":"idea-bio2-protein-plus-training-during-io","kind":"idea","name":"Test protein and resistance training during immunotherapy","route":"/ideas/idea-bio2-protein-plus-training-during-io/","maturity":"speculative","tldr":"Muscle is an immune organ as well as a movement organ. Building it during immunotherapy might improve how well the treatment works, not just how patients feel.","via":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]},{"id":"idea-acc-eml-listing-price-commitments","kind":"idea","name":"Tie WHO essential-medicines listing to a published tiered price and supply pledge","route":"/ideas/idea-acc-eml-listing-price-commitments/","maturity":"speculative","tldr":"When a cancer drug is added to the WHO essential medicines list, the maker should publicly commit to a low price and reliable supply for poorer countries, or the listing is withheld.","via":[{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}]}],"manufacturing":{"sites":[{"id":"abzena-sanford","name":"Abzena Sanford","operator":"Abzena","operatorRoute":"/companies/abzena/","ownership":"cdmo","city":"Sanford, North Carolina","country":"US","capabilities":["adc-conjugation","antibody-drug-substance"],"capabilityLabels":["ADC conjugation","Antibody drug substance"],"drugs":[],"source":{"label":"Abzena","url":"https://www.abzena.com/"}},{"id":"bms-devens","name":"Bristol Myers Squibb Devens","operator":"Bristol Myers Squibb","operatorRoute":"/companies/bms/","ownership":"in-house","city":"Devens, Massachusetts","country":"US","capabilities":["cell-therapy","antibody-drug-substance"],"capabilityLabels":["Cell therapy","Antibody drug substance"],"drugs":[{"id":"idecabtagene-vicleucel","kind":"drug","name":"Idecabtagene vicleucel","route":"/drugs/idecabtagene-vicleucel/"},{"id":"lisocabtagene-maraleucel","kind":"drug","name":"Lisocabtagene maraleucel","route":"/drugs/lisocabtagene-maraleucel/"}],"source":{"label":"BMS manufacturing","url":"https://www.bms.com/"}},{"id":"catalent-bloomington","name":"Catalent Bloomington","operator":"Catalent (Novo Holdings)","operatorRoute":"/companies/catalent/","ownership":"cdmo","city":"Bloomington, Indiana","country":"US","capabilities":["antibody-drug-substance","fill-finish"],"capabilityLabels":["Antibody drug substance","Fill and finish"],"drugs":[],"source":{"label":"Catalent Biologics","url":"https://biologics.catalent.com/"}},{"id":"fujifilm-holly-springs","name":"FUJIFILM Diosynth Holly Springs","operator":"FUJIFILM Diosynth Biotechnologies","operatorRoute":"/companies/fujifilm-diosynth/","ownership":"cdmo","city":"Holly Springs, North Carolina","country":"US","capabilities":["antibody-drug-substance","fill-finish"],"capabilityLabels":["Antibody drug substance","Fill and finish"],"drugs":[],"source":{"label":"FUJIFILM Diosynth Biotechnologies","url":"https://fujifilmdiosynth.com/"}},{"id":"lonza-visp","name":"Lonza Visp","operator":"Lonza","operatorRoute":"/companies/lonza/","ownership":"cdmo","city":"Visp","country":"CH","capabilities":["adc-conjugation","payload-linker","antibody-drug-substance"],"capabilityLabels":["ADC conjugation","Payload and linker chemistry","Antibody drug substance"],"drugs":[],"source":{"label":"Lonza bioconjugates","url":"https://www.lonza.com/bioconjugates"}},{"id":"samsung-biologics-songdo-adc","name":"Samsung Biologics ADC facility","operator":"Samsung Biologics","operatorRoute":"/companies/samsung-biologics/","ownership":"cdmo","city":"Incheon (Songdo)","country":"KR","capabilities":["adc-conjugation","antibody-drug-substance"],"capabilityLabels":["ADC conjugation","Antibody drug substance"],"drugs":[],"source":{"label":"Samsung Biologics","url":"https://samsungbiologics.com/"}},{"id":"wuxi-xdc-wuxi","name":"WuXi XDC Wuxi","operator":"WuXi XDC","operatorRoute":"/companies/wuxi-xdc/","ownership":"cdmo","city":"Wuxi","country":"CN","capabilities":["adc-conjugation","payload-linker","antibody-drug-substance","fill-finish"],"capabilityLabels":["ADC conjugation","Payload and linker chemistry","Antibody drug substance","Fill and finish"],"drugs":[],"source":{"label":"WuXi XDC","url":"https://www.wuxixdc.com/"}}],"capabilities":["Antibody drug substance"],"chain":{"id":"biologics","name":"Biologics: antibodies and biosimilars","summary":"CHO cell culture, Protein A purification, single-use plants and fill-finish, and the biosimilar copies that cut prices.","route":"/manufacturing/#chain-biologics","technologies":[{"id":"monoclonal-antibody-manufacturing","kind":"technology","name":"Antibody manufacturing (CHO bioprocessing)","route":"/technologies/monoclonal-antibody-manufacturing/"},{"id":"downstream-purification-chromatography","kind":"technology","name":"Downstream purification (Protein A capture, viral clearance, polishing)","route":"/technologies/downstream-purification-chromatography/"},{"id":"single-use-bioprocessing","kind":"technology","name":"Single-use bioprocessing systems","route":"/technologies/single-use-bioprocessing/"},{"id":"sterile-fill-finish","kind":"technology","name":"Sterile fill-finish and lyophilisation","route":"/technologies/sterile-fill-finish/"},{"id":"biosimilar-manufacturing","kind":"technology","name":"Biosimilar manufacturing and comparability","route":"/technologies/biosimilar-manufacturing/"}],"companies":[{"id":"samsung-biologics","kind":"company","name":"Samsung Biologics","route":"/companies/samsung-biologics/"},{"id":"lonza","kind":"company","name":"Lonza","route":"/companies/lonza/"},{"id":"wuxi-biologics","kind":"company","name":"WuXi Biologics","route":"/companies/wuxi-biologics/"},{"id":"fujifilm-diosynth","kind":"company","name":"FUJIFILM Diosynth Biotechnologies","route":"/companies/fujifilm-diosynth/"},{"id":"boehringer-ingelheim-biox","kind":"company","name":"Boehringer Ingelheim BioXcellence","route":"/companies/boehringer-ingelheim-biox/"},{"id":"thermo-fisher","kind":"company","name":"Thermo Fisher Scientific","route":"/companies/thermo-fisher/"},{"id":"catalent","kind":"company","name":"Catalent (Novo Holdings)","route":"/companies/catalent/"},{"id":"cytiva","kind":"company","name":"Cytiva (Danaher)","route":"/companies/cytiva/"},{"id":"sartorius","kind":"company","name":"Sartorius","route":"/companies/sartorius/"},{"id":"merck-kgaa","kind":"company","name":"Merck KGaA (EMD Serono)","route":"/companies/merck-kgaa/"},{"id":"celltrion","kind":"company","name":"Celltrion","route":"/companies/celltrion/"},{"id":"samsung-bioepis","kind":"company","name":"Samsung Bioepis","route":"/companies/samsung-bioepis/"},{"id":"biocon","kind":"company","name":"Biocon","route":"/companies/biocon/"},{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}],"products":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"filgrastim","kind":"drug","name":"Filgrastim (G-CSF)","route":"/drugs/filgrastim/"},{"id":"pegfilgrastim","kind":"drug","name":"Pegfilgrastim","route":"/drugs/pegfilgrastim/"}]},"technologies":[{"id":"monoclonal-antibody-manufacturing","kind":"technology","name":"Antibody manufacturing (CHO bioprocessing)","route":"/technologies/monoclonal-antibody-manufacturing/","tldr":"Antibody manufacturing means growing antibody drugs like pembrolizumab or trastuzumab in vats of engineered hamster cells, then purifying them. It is the industrial base for most modern cancer 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section is read from existing corpus records and names them (from, via, exemplars, refs); a section with nothing behind it is empty. Medicines of a format are the open drug engine's (/pipeline/engine/); technologies are listed in src/lib/modular-formats.ts. CC BY-NC 4.0, attribute Data from OnCo (onco.cc). Not medical advice."}