2012 in oncology

The approvals rows on treatment records: region, year and indication.

• 2012Abiraterone acetate approved in US

  mCRPC pre-chemotherapy

• 2012Axitinib approved in US

  Advanced RCC after one prior systemic therapy

• 2012Bosutinib approved in US

  Ph+ CML after prior TKI

• 2012Cabozantinib approved in US

  Medullary thyroid cancer (Cometriq)

• 2012Carfilzomib approved in US

  Relapsed myeloma (accelerated)

• 2012Choline C-11 approved in US

  PET imaging of suspected prostate cancer recurrence with non-informative conventional imaging

• 2012Crizotinib approved in EU

  Conditional Oct 2012; full approval 2015

• 2012Decitabine approved in EU

  Newly diagnosed de novo or secondary AML in adults 65 and over not candidates for standard induction

• 2012Enzalutamide approved in US

  mCRPC after docetaxel (pre-chemo 2014)

• 2012Everolimus approved in US

  HR+/HER2- advanced breast cancer with exemestane after NSAI failure

• 2012Glucarpidase approved in US

  Toxic plasma methotrexate concentrations with delayed clearance due to impaired renal function

• 2012Granisetron approved in EU

  Transdermal granisetron for moderately or highly emetogenic chemotherapy (Sancuso)

• 2012Mercaptopurine approved in EU

  ALL in adults, adolescents and children (Xaluprine oral suspension)

• 2012Mogamulizumab approved in JP

  Relapsed CCR4+ adult T-cell leukaemia/lymphoma; later PTCL/CTCL

• 2012Omacetaxine mepesuccinate approved in US

  Chronic or accelerated phase CML resistant or intolerant to two or more TKIs (accelerated; full approval 2014)

• 2012Pasireotide approved in US

  Cushing's disease when pituitary surgery is not an option or has not been curative

• 2012Pazopanib approved in US

  Advanced non-adipocytic soft-tissue sarcoma after chemotherapy

• 2012Pertuzumab approved in US

  First-line HER2+ metastatic breast cancer with trastuzumab and docetaxel

• 2012Pixantrone approved in EU

  Multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphoma, single agent (conditional). Authorisation expired 12 June 2024; the holder did not apply for renewal

• 2012Ponatinib approved in US

  CML and Ph+ ALL resistant to prior TKIs or with T315I

• 2012Prosigna (PAM50) approved in EU

  CE-IVD

• 2012Regorafenib approved in US

  Metastatic colorectal cancer, previously treated

• 2012Regorafenib approved in US

  Metastatic colorectal cancer after fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF and, if RAS wild-type, anti-EGFR therapy. Approved September 2012 on CORRECT.

• 2012Ruxolitinib approved in EU

  Myelofibrosis

• 2012therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF) approved in US

  therascreen KRAS: cetuximab and panitumumab eligibility in metastatic colorectal cancer

• 2012Vismodegib approved in US

  Metastatic BCC or locally advanced BCC recurrent after surgery or not amenable to surgery/radiation

• 2012Ziv-aflibercept approved in US

  Metastatic colorectal cancer resistant to or progressing after oxaliplatin, with FOLFIRI

• 2012Ziv-aflibercept approved in US

  Metastatic colorectal cancer resistant to or progressing after an oxaliplatin-containing regimen, with FOLFIRI. Approved August 2012 on VELOUR.

The regulatory events on treatment records: designations, filings, decisions, label changes and withdrawals, most of them carrying a full date.

• 8 June 2012Pertuzumab: approval (US)

  First-line metastatic (CLEOPATRA)

• July 2012Cetuximab: label change (US)

  Label restricted to KRAS wild-type; first-line FOLFIRI indication (CRYSTAL)

• 14 December 2012Ponatinib: approval (US)

  Resistant CML/Ph+ ALL

The statutes, regulations, guidance and court rulings in the law index, dated to the year the instrument was made.

• 2012Breakthrough Therapy / Priority Review / Priority Voucher

  United States, guidance.

• 2012FDASIA 2012 and the origins of the expedited programmes

  United States, statute.

• 2012Nexavar compulsory licence (India, 2012)

  India, court ruling.

The year reported on trial records, with the headline result the record gives.

• 2012A Trial of Intravenous Denileukin Diftitox in Stage III or IV Ovarian Cancer reported
  Ovarian cancerDenileukin diftitox
• 2012AEWS0031 reported

  Five-year event-free survival 73 percent with two-weekly (interval-compressed) chemotherapy against 65 percent with three-weekly chemotherapy (p 0.048), with similar toxicity.

  Ewing sarcomaSarcomas (soft tissue, bone, GIST)Childhood cancers (all types)Vincristine
• 2012AFFIRM reported

  Median overall survival 18.4 against 13.6 months (hazard ratio 0.63, 95 percent confidence interval 0.53 to 0.75) after docetaxel; PSA fall of 50 percent or more in 54 against 2 pe...

  Prostate cancerMetastatic castration-resistant prostate cancerEnzalutamide
• 2012ALFA-0701 reported

  EFS 17.3 vs 9.5 months; HR 0.56.

  Acute myeloid leukaemiaGemtuzumab ozogamicinCytarabine + anthracycline ('7+3')
• 2012Alliance N0147 reported

  Three-year disease-free survival 71.5 with cetuximab against 74.6 percent without, in KRAS wild-type disease.

  Colorectal cancerColon cancer (adenocarcinoma of the colon)CetuximabFOLFOX (5-FU, leucovorin, oxaliplatin)
• 2012BOLERO-2 reported

  Everolimus plus exemestane more than doubled progression-free survival compared with exemestane alone; approved in July 2012.

  HR-positive / HER2-negative breast cancerHR-positive metastatic breast cancer after CDK4/6 inhibitorsBreast cancer (all types)Everolimus
• 2012CALGB 90401 reported

  Median overall survival 22.6 against 21.5 months (hazard ratio 0.91, 95 percent confidence interval 0.78 to 1.05, p=0.181) despite progression-free survival 9.9 against 7.5 months...

  Prostate cancerMetastatic castration-resistant prostate cancerBevacizumabDocetaxel
• 2012Cediranib (AZD2171, RECENTIN™) in Addition to Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer reported
  Colorectal cancerCediranibFOLFOX (5-FU, leucovorin, oxaliplatin)Leucovorin (folinic acid)
• 2012Cediranib in Combination With Lomustine Chemotherapy in Recurrent Glioblastoma reported
  Glioma & glioblastomaCediranib
• 2012CLASSIC reported

  Three-year disease-free survival 74 percent with adjuvant CAPOX against 59 percent with surgery alone (hazard ratio 0.56, p < 0.0001); five-year overall survival 78 against 69 perc...

  Gastric & gastro-oesophageal junction cancerCapecitabineOxaliplatin
• 2012COMFORT-I reported

  Spleen volume reduction of 35 percent or more at 24 weeks in 41.9 percent of patients on ruxolitinib against 0.7 percent on placebo; approved in the United States in November 2011.

  Primary myelofibrosisMyeloproliferative neoplasms (PV, ET, myelofibrosis)Ruxolitinib
• 2012COMFORT-II reported

  Spleen volume reduction of at least 35 percent at week 48 in 28 percent of patients on ruxolitinib against 0 percent on best available therapy; European approval in 2012.

  Primary myelofibrosisMyeloproliferative neoplasms (PV, ET, myelofibrosis)Ruxolitinib
• 2012CROSS reported

  10-year OS 38% vs 25%; median OS 49.4 vs 24.0 months.

  Oesophageal cancerOesophageal squamous cell carcinomaOesophageal and junctional adenocarcinomaGastric & gastro-oesophageal junction cancer
• 2012ENTHUSE M1 reported

  Median overall survival 24.5 against 22.5 months (hazard ratio 0.87, 95.2 percent confidence interval 0.69 to 1.10, p=0.240): not significant, with peripheral oedema in 44 percent...

  Prostate cancerMetastatic castration-resistant prostate cancerZibotentan
• 2012EORTC 10801 reported

  At a median 22.1 years, time to distant metastasis hazard ratio 1.13 (0.92 to 1.38) and time to death 1.11 (0.94 to 1.33) for conservation against mastectomy; twenty-year overall s...

  Breast cancer (all types)HR-positive / HER2-negative breast cancerHER2-positive breast cancerTriple-negative breast cancer (TNBC)
• 2012EORTC 22911 reported

  Biochemical progression-free survival hazard ratio 0.49 (95 percent confidence interval 0.41 to 0.59) at a median 10.6 years, but no maintained clinical progression-free survival b...

  Prostate cancerLocalised prostate cancer, high and very high riskBiochemical recurrence of prostate cancer
• 2012ERIVANCE BCC reported

  Objective response 43% in locally advanced and 30% in metastatic basal cell carcinoma (independent review).

  Locally advanced and metastatic basal cell carcinomaBasal cell carcinomaSkin cancer (all types)Vismodegib
• 2012EXAM reported

  Cabozantinib lengthened progression-free survival compared with placebo in progressive medullary thyroid cancer; approved in November 2012.

  Medullary thyroid cancerThyroid cancerCabozantinib
• 2012HiLo reported

  Ablation success 85.0% (1.1 GBq) vs 88.9% (3.7 GBq), non-inferior.

  Thyroid cancer
• 2012I-SPY 1 (CALGB 150007/150012, ACRIN 6657) reported

  Pathological complete response and early MRI volume change predicted recurrence-free survival, most strongly in triple-negative, HER2-positive and MammaPrint high-risk tumours.

  Breast cancer (all types)Triple-negative breast cancer (TNBC)HER2-positive breast cancerPaclitaxel / nab-paclitaxel
• 2012Investigation of the Effect of Degarelix in Terms of Prostate Volume Reduction in Prostate Cancer Patients reported
  Prostate cancerDegarelixGoserelin / leuprolide (ovarian function suppression)Bicalutamide
• 2012MoleMate UK Trial reported

  No difference in the appropriateness of referral (56.8 percent against 64.5 percent) and more lesions referred with the device (29.8 percent against 22.4 percent) (BMJ 2012).

  MelanomaSkin cancer (all types)
• 2012National Polyp Study reported

  Standardised incidence-based mortality ratio 0.47 (95% CI 0.26 to 0.80) after polypectomy, a 53 percent reduction in deaths from colorectal cancer.

  Colorectal cancer
• 2012Neoadjuvant Study Investigating Degarelix in Patients Suffering From Prostate Cancer reported
  Prostate cancerDegarelixGoserelin / leuprolide (ovarian function suppression)Bicalutamide
• 2012NeoSphere reported

  Pertuzumab added to trastuzumab and docetaxel raised the pathological complete response rate in HER2-positive breast cancer; neoadjuvant pertuzumab received accelerated approval in...

  Early HER2-positive breast cancerHER2-positive breast cancerPertuzumabTrastuzumab
• 2012NOA-08 reported

  Median overall survival 8.6 months with temozolomide against 9.6 months with radiotherapy (hazard ratio 1.09, non-inferior); MGMT-methylated tumours did better with temozolomide an...

  Glioma & glioblastomaAstrocytoma, IDH-mutant (grades 2 to 4)Brain and spinal cord tumours (all types)Temozolomide
• 2012Safety and Efficacy Study of Catumaxomab to Treat Ovarian Cancer After a Complete Response to Chemotherapy reported
  Ovarian cancerCatumaxomab
• 2012SSGXVIII/AIO (adjuvant imatinib in GIST) reported

  RFS HR 0.46; OS HR 0.45 (5 years).

  Sarcomas (soft tissue, bone, GIST)Imatinib
• 2012Study to Compare the Efficacy and Safety of Olaparib When Given in Combination With Carboplatin and Paclitaxel, Compared With Carboplatin and Paclitax reported
  Ovarian cancerPlatinum-sensitive ovarian cancerOlaparibPaclitaxel / nab-paclitaxel
• 2012TIME2 reported

  No significant difference in breathlessness over 42 days (24.7 against 24.4 mm on a 100 mm scale, difference 0.16 mm, p=0.96); fewer hospital days with the catheter.

  Non-small-cell lung cancerSmall-cell lung cancerLung cancer (all types)Pleural mesothelioma
• 2012TUMORAPA (switching from a calcineurin inhibitor to sirolimus after a transplant skin cancer) reported

  New cutaneous squamous cell carcinoma in 22 per cent of patients switched to sirolimus against 39 per cent continuing calcineurin inhibitors (relative risk 0.56, 95 per cent confid...

  Cutaneous squamous cell carcinomaSkin cancer (all types)Sirolimus
• 2012VELOUR reported

  Median overall survival 13.50 against 12.06 months (hazard ratio 0.817).

  Colorectal cancerZiv-afliberceptFOLFIRI (5-FU, leucovorin, irinotecan)Irinotecan (and liposomal irinotecan)
• 2012ZETA reported

  Vandetanib prolonged progression-free survival over placebo in advanced medullary thyroid cancer; approved in April 2011 as the first drug for the disease.

  Medullary thyroid cancerThyroid cancerVandetanib

The publication year on key paper records.

• 2012Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind...

  Fizazi K, Scher HI, Molina A, et al. The Lancet Oncology.

• 2012Accessories to the crime: functions of cells recruited to the tumor microenvironment

  Hanahan D, Coussens LM. Cancer Cell.

• 2012AEWS0031: randomised trial of interval-compressed chemotherapy for localised Ewing sarcoma

  Womer RB, West DC, Krailo MD, et al. Journal of Clinical Oncology.

• 2012AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapy

  Scher HI, Fizazi K, Saad F, et al. New England Journal of Medicine.

• 2012ANBL00P2: expectant observation as primary therapy for neuroblastoma in young infants

  Nuchtern JG, London WB, Barnewolt CE, et al. Annals of Surgery.

• 2012Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal invasion in gastric cancer: a meta-analysis of the randomized controlled trials

  Sun J, Song Y, Wang Z, et al. BMC cancer.

• 2012Cancer: a de-repression of a default survival program common to all cells?: a life-history perspective on the nature of cancer

  Vincent M. BioEssays.

• 2012Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors

  Stylianopoulos T, Martin JD, Chauhan VP, et al. Proceedings of the National Academy of Sciences.

• 2012CLASSIC: adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy

  Bang YJ, Kim YW, Yang HK, et al. The Lancet.

• 2012Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)

  Thakker RV, Newey PJ, Walls GV, et al. The Journal of clinical endocrinology and metabolism.

• 2012Clonal evolution in cancer

  Greaves M, Maley CC. Nature.

• 2012COG P9641: surgery alone or with restricted chemotherapy for low-risk neuroblastoma

  Strother DR, London WB, Schmidt ML, et al. Journal of Clinical Oncology.

• 2012Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths (National Polyp Study)

  Zauber AG, Winawer SJ, O'Brien MJ, et al. New England Journal of Medicine.

• 2012COMFORT-I: ruxolitinib, the first JAK inhibitor, versus placebo for myelofibrosis

  Verstovsek S, Mesa RA, Gotlib J, et al. New England Journal of Medicine.

• 2012COMFORT-II: JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis

  Harrison C, Kiladjian JJ, Al-Ali HK, et al. New England Journal of Medicine.

• 2012Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials

  Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Peto R, Davies C, et al. The Lancet.

• 2012Comprehensive genomic characterization of squamous cell lung cancers

  Cancer Genome Atlas Research Network. Nature.

• 2012Comprehensive molecular characterization of human colon and rectal cancer

  Cancer Genome Atlas Network. Nature.

• 2012Comprehensive molecular portraits of human breast tumours

  Cancer Genome Atlas Network. Nature.

• 2012CROSS: preoperative chemoradiotherapy for oesophageal or junctional cancer

  van Hagen P, Hulshof MC, van Lanschot JJ, et al. New England Journal of Medicine.

• 2012Drug development: Raise standards for preclinical cancer research

  Begley CG, Ellis LM. Nature.

• 2012Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermi...

  Chua TC, Moran BJ, Sugarbaker PH, et al. Journal of Clinical Oncology.

• 2012Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarci...

  Neoptolemos JP, Moore MJ, Cox TF, et al. JAMA.

• 2012Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a...

  Gianni L, Pienkowski T, Im YH, et al. The Lancet Oncology.

• 2012Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer

  Misale S, Yaeger R, Hobor S, et al. Nature.

• 2012ERIVANCE BCC: efficacy and safety of vismodegib in advanced basal cell carcinoma

  Sekulic A, Migden MR, Oro AE, et al. New England Journal of Medicine.

• 2012Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a...

  Rosell R, Carcereny E, Gervais R, et al. The Lancet Oncology.

• 2012EsPhALL: imatinib after induction for children and adolescents with Philadelphia chromosome-positive acute lymphoblastic leukaemia

  Biondi A, Schrappe M, De Lorenzo P, et al. The Lancet Oncology.

• 2012Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer

  Baselga J, Campone M, Piccart M, et al. New England Journal of Medicine.

• 2012Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer

  Barbieri CE, Baca SC, Lawrence MS, et al. Nature Genetics.

• 2012FIRM-ACT: combination chemotherapy in advanced adrenocortical carcinoma

  Fassnacht M, Terzolo M, Allolio B, et al. New England Journal of Medicine.

• 2012Gerlinger: a single biopsy misses most of the mutations in a kidney tumour

  Gerlinger M, Rowan AJ, Horswell S, et al. New England Journal of Medicine.

• 2012Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients

  Ryan JL, Heckler CE, Roscoe JA, et al. Supportive care in cancer.

• 2012Identification of Lynch syndrome among patients with colorectal cancer

  Moreira L, Balaguer F, Lindor N, et al. JAMA.

• 2012Intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are at least 1.0 cm): clinicop...

  Adsay V, Jang KT, Roa JC, et al. American Journal of Surgical Pathology.

• 2012La Rosa 2012: clinicopathologic study of 62 acinar cell carcinomas of the pancreas

  La Rosa S, Adsay V, Albarello L, et al. American Journal of Surgical Pathology.

• 2012Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials

  Seely D, Wu P, Fritz H, et al. Integrative cancer therapies.

• 2012Molecular subgroups of medulloblastoma: the current consensus

  Taylor MD, Northcott PA, Korshunov A, et al. Acta Neuropathologica.

• 2012MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition

  Horiuchi D, Kusdra L, Huskey NE, et al. Journal of Experimental Medicine.

• 2012NOA-08: temozolomide alone versus radiotherapy alone for malignant astrocytoma in the elderly

  Wick W, Platten M, Meisner C, et al. The Lancet Oncology.

• 2012Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

  Biankin AV, Waddell N, Kassahn KS, et al. Nature.

• 2012Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy

  Pardoll DM. Nature Reviews Cancer.

• 2012Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer

  Baselga J, Cortés J, Kim SB, et al. New England Journal of Medicine.

• 2012Pre-operative nutrition support in patients undergoing gastrointestinal surgery

  Burden S, Todd C, Hill J, et al. The Cochrane database of systematic reviews.

• 2012Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia

  Kanda M, Matthaei H, Wu J, et al. Gastroenterology.

• 2012Publication of NIH funded trials registered in ClinicalTrials.gov: cross sectional analysis

  Ross JS, Tse T, Zarin DA, et al. BMJ.

• 2012Recurrent R-spondin fusions in colon cancer

  Seshagiri S, Stawiski EW, Durinck S, et al. Nature.

• 2012Regulatory review of novel therapeutics--comparison of three regulatory agencies

  Downing NS, Aminawung JA, Shah ND, et al. New England Journal of Medicine.

• 2012ROS1 rearrangements define a unique molecular class of lung cancers

  Bergethon K, Shaw AT, Ou SH, et al. Journal of Clinical Oncology.

• 2012Russell, Peng and Bell 2012: the field states its own problems

  Russell SJ, Peng KW, Bell JC. Nature Biotechnology.

• 2012Safety and activity of anti-PD-L1 antibody in patients with advanced cancer

  Brahmer JR, Tykodi SS, Chow LQ, et al. New England Journal of Medicine.

• 2012Screening older cancer patients: first evaluation of the G-8 geriatric screening tool

  Bellera CA, Rainfray M, Mathoulin-Pélissier S, et al. Annals of Oncology.

• 2012Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective internati...

  Trappe R, Oertel S, Leblond V, et al. The Lancet Oncology.

• 2012Siegel 2012: Cancer statistics, 2012

  Siegel R, Naishadham D, Jemal A. CA: A Cancer Journal for Clinicians.

• 2012Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women

  Nechuta SJ, Caan BJ, Chen WY, et al. The American journal of clinical nutrition.

• 2012SSG XVIII/AIO: one versus three years of adjuvant imatinib for operable gastrointestinal stromal tumour

  Joensuu H, Eriksson M, Sundby Hall K, et al. JAMA.

• 2012Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised...

  Malmström A, Grønberg BH, Marosi C, et al. The Lancet Oncology.

• 2012The benefits and harms of breast cancer screening: an independent review

  Independent UK Panel on Breast Cancer Screening. The Lancet.

• 2012The clonal and mutational evolution spectrum of primary triple-negative breast cancers

  Shah SP, Roth A, Goya R, et al. Nature.

• 2012The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers

  Diaz LA, Williams RT, Wu J, et al. Nature.

• 2012The mutational landscape of lethal castration-resistant prostate cancer

  Grasso CS, Wu YM, Robinson DR, et al. Nature.

• 2012The TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes: a cohort study and meta-analysis

  Pettersson A, Graff RE, Bauer SR, et al. Cancer Epidemiology, Biomarkers and Prevention.

• 2012Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer

  Topalian SL, Hodi FS, Brahmer JR, et al. New England Journal of Medicine.

• 2012USPSTF 2012: screening for prostate cancer, recommendation statement (grade D)

  Moyer VA, U.S. Preventive Services Task Force. Annals of Internal Medicine.

• 2012ZETA: vandetanib in locally advanced or metastatic medullary thyroid cancer

  Wells SA, Robinson BG, Gagel RF, et al. Journal of Clinical Oncology.

The history entries editors wrote on cancer records: the dated turning points of each disease.

• 2012AEWS0031: interval compression improves EFS (Womer, JCO)

  Ewing sarcoma

• 2012ALFA-0701 rescues gemtuzumab

  Acute myeloid leukaemia. Fractionated dosing with 7+3 improves EFS; re-approval 2017.

  ALFA-0701Gemtuzumab ozogamicin
• 2012Axitinib approved (AXIS)

  Renal cell carcinoma

  Axitinib
• 2012BOLERO-2: everolimus with exemestane after an aromatase inhibitor

  HR-positive metastatic breast cancer after CDK4/6 inhibitors

  EverolimusExemestane
• 2012BRAF V600E found in ECD and LCH

  Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms. Haroche and colleagues (Blood 2012) after Badalian-Very's LCH discovery (2010).

  BRAF
• 2012BRAF V600E found in more than half of patients

  Erdheim-Chester disease

  BRAFBRAF V600E mutation
• 2012Cabozantinib approved (EXAM trial)

  Medullary thyroid cancer

  Cabozantinib
• 2012Carfilzomib approved; International Staging refined

  Multiple myeloma

  Carfilzomib
• 2012Carfilzomib approved; pomalidomide follows in 2013

  Relapsed or refractory multiple myeloma

  CarfilzomibPomalidomide
• 2012Consensus on four molecular groups; group 3 and group 4 named

  Group 3 and group 4 medulloblastoma (non-WNT/non-SHH)

• 2012Consensus on four molecular groups: WNT, SHH, group 3 and group 4

  WNT-activated medulloblastoma

• 2012CROSS chemoradiation before surgery

  Oesophageal and junctional adenocarcinoma

  CROSS
• 2012CROSS: chemoradiation before surgery doubles survival

  Oesophageal squamous cell carcinoma

  CROSS
• 2012CROSS: neoadjuvant chemoradiation

  Oesophageal cancer

• 2012CROSS: neoadjuvant chemoradiation becomes standard

  Oesophageal cancer

  CROSS
• 2012Enzalutamide approved

  Metastatic castration-resistant prostate cancer

  Enzalutamide
• 2012EORTC 62931: adjuvant doxorubicin-ifosfamide does not improve survival

  Soft tissue sarcoma of the extremity (localised and advanced)

  DoxorubicinIfosfamide
• 2012ERIVANCE: vismodegib approved, the first hedgehog inhibitor

  Locally advanced and metastatic basal cell carcinoma

  ERIVANCE BCCVismodegib
• 2012ESPAC-3 periampullary

  Ampullary cancer (ampulla of Vater). Adjuvant chemotherapy after resection of periampullary cancer; survival benefit in adjusted analysis.

  Gemcitabine
• 2012Everolimus + exemestane (BOLERO-2)

  HR-positive / HER2-negative breast cancer. First targeted agent to overcome endocrine resistance.

  Everolimus
• 2012Everolimus regresses cardiac rhabdomyoma in tuberous sclerosis

  Rare cancers of childhood (NCI PDQ umbrella). Case series lead to medical management replacing surgery.

  Everolimus
• 2012FIRM-ACT: EDP-M beats streptozocin-mitotane on response and progression-free survival

  Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable)

  EtoposideDoxorubicinCisplatinMitotane
• 2012FIRM-ACT: EDP-M vs streptozocin-mitotane (NEJM)

  Adrenocortical carcinoma

  EtoposideDoxorubicinCisplatinMitotane
• 2012First CAR-T cures: Emily Whitehead

  Acute lymphoblastic leukaemia. CTL019 at CHOP/Penn; durable remission of refractory paediatric ALL.

  Tisagenlecleucel
• 2012Four molecular subgroups agreed (Taylor et al., Acta Neuropathol)

  Medulloblastoma

• 2012Fukuoka guidelines introduce high-risk stigmata and worrisome features

  Intraductal papillary mucinous neoplasm and other pancreatic cystic precursors

  MRIEndoscopic ultrasound and EBUS systems
• 2012Genomic landscape: ID3, TCF3 and CCND3

  Burkitt lymphoma. Schmitz and Richter (Nature, Nature Genetics) define the cooperating mutations.

• 2012Global BCG shortage begins after Sanofi production halt

  Bladder & urothelial cancer

  Intravesical BCG
• 2012GOG-0209: carboplatin-paclitaxel as effective as and less toxic than TAP

  Advanced or recurrent endometrial cancer

  CarboplatinPaclitaxel / nab-paclitaxel
• 2012H3 K27M mutation discovered

  Diffuse midline glioma, H3 K27-altered (including DIPG). Schwartzentruber and Wu (Nature Genetics) find recurrent histone H3 mutations in DIPG and paediatric glioblastoma.

  H3 K27M (diffuse midline glioma)
• 2012HiLo and ESTIMABL1: low-dose radioiodine ablation is enough

  Thyroid cancer

  HiLo
• 2012Histone H3 mutations discovered in paediatric glioma

  Paediatric high-grade glioma (excluding diffuse midline glioma). Schwartzentruber and colleagues (Nature) and Wu and colleagues (Nature Genetics) find H3.3 K27M and G34 mutations.

• 2012Imatinib phase 2 in advanced chordoma

  Chordoma. Stacchiotti and colleagues: disease stabilisation in most patients, few objective responses.

  Imatinib
• 2012International registry of 2,298 patients: median survival 16.3 years after cytoreduction and HIPEC

  Low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei

  HIPEC / PIPAC (intraperitoneal chemotherapy)
• 2012Intravitreal melphalan for vitreous seeds (Munier)

  Retinoblastoma

  Melphalan (including hepatic delivery system)
• 2012IPSS-R

  Myelodysplastic syndromes / neoplasms (MDS). Revised score with five cytogenetic groups and refined thresholds.

• 2012IPSS-R revised scoring system

  Lower-risk myelodysplastic syndromes

  Disease-specific staging and risk systems (FIGO, Ann Arbor, IPI, R-ISS, ELN, IMDC)
• 2012JAZF1-SUZ12 and YWHAE-NUTM2 fusions define low- and high-grade ESS

  Uterine sarcoma. Lee and colleagues; earlier Koontz 2001 for JAZF1.

• 2012Lenalidomide maintenance after transplant lengthens remission (IFM 2005-02, CALGB 100104)

  Newly diagnosed multiple myeloma, transplant-eligible

  Lenalidomide
• 2012Lower Anogenital Squamous Terminology (LAST) unifies HSIL and LSIL across anogenital sites

  Anal high-grade squamous intraepithelial lesions (precursor)

  HPV-positive (p16) head and neck cancer
• 2012Metastasis-free survival validated as a surrogate for survival in prostate cancer

  Non-metastatic castration-resistant prostate cancer

  Castration-resistant prostate cancer (CRPC)
• 2012Multi-institutional CRS-HIPEC outcomes: 10-year survival 63% (Chua, JCO)

  Appendiceal cancer and pseudomyxoma peritonei

  HIPEC / PIPAC (intraperitoneal chemotherapy)
• 2012MYD88 L265P discovered

  Waldenström macroglobulinaemia. Treon et al. (NEJM): whole-genome sequencing finds the mutation in over 90% of WM.

  BTK (Bruton tyrosine kinase)
• 2012NCCN publishes the first adolescent and young adult oncology guidelines

  Adolescent and young adult cancers (ages 15 to 39)

• 2012NeoSphere: pertuzumab raises pathological complete response

  Early HER2-positive breast cancer

  Pertuzumab
• 2012P9641: surgery alone gives 97 percent survival in low-risk disease; expectant observation of small adrenal masses reported

  Low-risk neuroblastoma (INRG very low and low risk, including stage MS)

  Active surveillance
• 2012Pazopanib approved for soft-tissue sarcoma including synovial sarcoma

  Synovial sarcoma

  Pazopanib
• 2012Pertuzumab and dual blockade (CLEOPATRA)

  HER2-positive breast cancer

  PertuzumabCLEOPATRA
• 2012Polypectomy prevents deaths, not just cancers

  Colorectal cancer. National Polyp Study at 23 years: colorectal cancer mortality halved against the general population.

  Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths (National Polyp Study)Comprehensive molecular characterization of human colon and rectal cancer
• 2012Ponatinib approved for advanced phase including T315I

  Chronic myeloid leukaemia, accelerated and blast phase

  Ponatinib
• 2012Ponatinib approved, covering T315I

  Chronic myeloid leukaemia, chronic phase

  Ponatinib
• 2012Ponatinib covers T315I; bosutinib approved

  Chronic myeloid leukaemia (CML)

  PonatinibBosutinib
• 2012PTLD-1: sequential rituximab then CHOP

  Post-transplant lymphoproliferative disorder (PTLD). Trappe and colleagues, Lancet Oncology 2012.

  Rituximab
• 2012Resistance to EGFR antibodies is selection, not mutation

  Colorectal cancer. KRAS-mutant clones emerge in plasma 5 to 6 months into panitumumab and are detectable up to 10 months before progression; modelling places them in the tumour bef...

  The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancersEmergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
• 2012RET fusions (KIF5B-RET) found in lung adenocarcinoma

  RET fusion-positive non-small-cell lung cancer

  RETGene fusion
• 2012Screening is recommended against, and enzalutamide arrives

  Prostate cancer. The United States task force issued a grade D recommendation against prostate-specific antigen screening at any age; it moved men aged 55 to 69 to grade C in 2018...

  USPSTF 2012: screening for prostate cancer, recommendation statement (grade D)USPSTF 2018: screening for prostate cancer, recommendation statement (grade C at 55 to 69, grade D at 70 and over)AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapyPREVAIL: enzalutamide in metastatic prostate cancer before chemotherapy
• 2012SEER analysis of 415 adenosquamous carcinomas defines the phenotype

  Adenosquamous carcinoma of the pancreas

  Grade
• 2012SSG XVIII: three years of adjuvant imatinib extends overall survival

  KIT exon 11-mutant GIST

  Imatinib
• 2012SSGXVIII: 3-year adjuvant imatinib; pazopanib approved (PALETTE)

  Sarcomas (soft tissue, bone, GIST)

  SSGXVIII/AIO (adjuvant imatinib in GIST)Pazopanib
• 2012SSGXVIII: three years of adjuvant imatinib improves overall survival

  Gastrointestinal stromal tumour (GIST)

  Imatinib
• 2012TCGA basal-like portrait and the first TNBC genomes

  Triple-negative breast cancer (TNBC). TP53 80%, PTEN loss 35%, RB1 loss 20% in basal-like disease and a likeness to serous ovarian cancer (Nature); Shah's 104 TNBC genomes show a c...

  Comprehensive molecular portraits of human breast tumoursThe clonal and mutational evolution spectrum of primary triple-negative breast cancersTP53
• 2012The fusion-negative half of the disease is named

  Prostate cancer. Exome sequencing of 112 tumours makes SPOP the commonest point mutation in prostate cancer and shows SPOP-mutant tumours never carry an ETS fusion; rapid-autopsy s...

  Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancerThe mutational landscape of lethal castration-resistant prostate cancerSPOPFOXA1
• 2012The molecular portrait, and a second way into WNT

  Colorectal cancer. TCGA read 276 tumours on every platform, found 16% hypermutated and added ARID1A, SOX9 and FAM123B to the driver list; the same year, R-spondin fusions were foun...

  Comprehensive molecular characterization of human colon and rectal cancerRecurrent R-spondin fusions in colon cancerRSPO3
• 2012The squamous genome read in full, and a second fusion class

  Non-small-cell lung cancer. TP53 mutated in nearly all of 178 squamous tumours, with the NFE2L2 and KEAP1 pathway altered in 34%, squamous differentiation genes in 44% and CDKN2A w...

  Comprehensive genomic characterization of squamous cell lung cancersROS1 rearrangements define a unique molecular class of lung cancersNFE2L2ROS1
• 2012TUMORAPA: changing the anti-rejection drug halves the next skin cancer

  Cutaneous squamous cell carcinoma. 120 kidney transplant recipients randomised; new squamous cell carcinomas in 22 per cent after a switch to sirolimus against 39 per cent continui...

  TUMORAPA (switching from a calcineurin inhibitor to sirolimus after a transplant skin cancer)
• 2012Vismodegib approved (ERIVANCE)

  Basal cell carcinoma. First hedgehog-pathway inhibitor.

  Vismodegib
• 2012Vismodegib approved for advanced basal cell carcinoma

  Skin cancer (all types). First hedgehog pathway inhibitor.

  Vismodegib

The since year on technology records: first use in humans or first approval, as the record states it.

• 2012G8 geriatric screening tool

  First use in humans or first approval, as the technology record states it.

• 2012Hedgehog pathway inhibitors

  First use in humans or first approval, as the technology record states it.

• 2012Multiparametric prostate MRI (PI-RADS)

  First use in humans or first approval, as the technology record states it.

• 2012Solid stress and tumour mechanobiology models

  First use in humans or first approval, as the technology record states it.

The founded year on company records.

• 2012Angiocrine Bioscience founded

  San Diego, CA

• 2012AskGene Pharma founded

  Camarillo

• 2012Atara Biotherapeutics founded

  Thousand Oaks, California

• 2012Avistone Biotechnology founded

  Beijing

• 2012Bpifrance founded

  Paris

• 2012ECOG-ACRIN Cancer Research Group founded

  Philadelphia, PA

• 2012Immix Biopharma founded

  Los Angeles, California

• 2012Intensity Therapeutics founded

  Shelton, Connecticut

• 2012Lightpoint Medical founded

  Chesham

• 2012LYSA (The Lymphoma Study Association) founded

  Pierre-Bénite (Lyon)

• 2012MobileODT founded

  Tel Aviv

• 2012NBE-Therapeutics founded

  Basel

• 2012Samsung Bioepis founded

  Incheon

• 2012Shanghai Bovax Biotechnology founded

  Shanghai

• 2012Shanghai Junshi Biosciences founded

  Shanghai

• 2012Syncona founded

  London

• 2012Universal DX founded

  Madrid

The founded year on journal records.

• 2012Cancer biology & medicine founded

  China Anti-Cancer Association and Tianjin Medical University Cancer Institute and Hospital

• 2012Cancer medicine founded

  Wiley

• 2012Chinese clinical oncology founded

  AME Publishing Company

• 2012CNS oncology founded

  Taylor & Francis

• 2012eLife founded

  eLife Sciences Publications

• 2012European thyroid journal founded

  Bioscientifica

• 2012Oncoimmunology founded

  Taylor & Francis

The selected publications each biography lists, which is a reading of that person rather than a reading of the year.

• 2012A phase II study of concurrent cetuximab–cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma

  Annals of Oncology

• 2012A randomized, double-blind, placebo-controlled trial of selective digestive decontamination using oral gentamicin and oral polymyxin E for eradication of carbap...

  Infect Control Hosp Epidemiol

• 2012Adoptive cell therapy for melanoma

  Cancer Journal

• 2012Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease

  American Journal of Respiratory and Critical Care Medicine

• 2012BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic c...

  Annals of Oncology

• 2012Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial

  JCO

• 2012Burkitt lymphoma in UGANDA, the legacy of Denis Burkitt and an update on the disease status

  British Journal of Haematology

• 2012Cancer cachexia: mediators, signaling, and metabolic pathways

  Cell Metabolism

• 2012Cancer immunotherapy via dendritic cells

  Nature Reviews Cancer

• 2012Central nervous system (CNS) tumor trends in children in a western Canadian province: a population-based 22-year retrospective study

  Journal of Neurology

• 2012Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations

  New England Journal of Medicine

• 2012Differential expression of sprouty genes in hepatocellular carcinoma

  Journal of Surgical Oncology

• 2012Differential oestrogen receptor binding is associated with clinical outcome in breast cancer

  Nature

• 2012Does longitudinal strain predict left ventricular remodeling after myocardial infarction?

  Echocardiography

• 2012Donor versus no-donor comparison of newly diagnosed myeloma patients included in the HOVON-50 multiple myeloma study

  Blood

• 2012Doxil, the first FDA-approved nano-drug: lessons learned

  Journal of Controlled Release

  Alberto Gabizon
• 2012EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib

  Cancer Discovery

• 2012ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making

  Annals of Oncology

• 2012Focal therapy for localised prostate cancer: a phase I/II trial

  Lancet Oncology

• 2012Genomic analysis identifies association of Fusobacterium with colorectal carcinoma

  Genome Research

• 2012Genomic landscape of non-small cell lung cancer in smokers and never-smokers

  Cell

• 2012Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model

  Proceedings of the National Academy of Sciences

• 2012Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial

  The Lancet Oncology

• 2012Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C

  Kidney International

• 2012Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the Children's Oncology Group

  JCO

• 2012Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients...

  Annals of Oncology

• 2012Increased survival with enzalutamide in prostate cancer after chemotherapy

  New England Journal of Medicine

• 2012Initial analysis of the International Association for the Study of Lung Cancer mesothelioma database

  Journal of Thoracic Oncology

• 2012JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis (COMFORT-II)

  NEJM

• 2012Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review

  Breast Cancer Res Treat

• 2012KIF5B-RET fusions in lung adenocarcinoma

  Nature Medicine

• 2012Metabolic regulation in pluripotent stem cells during reprogramming and self-renewal

  Cell Stem Cell

• 2012MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients

  Radiation Oncology

• 2012Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte-macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage...

  JCO

• 2012MYD88 L265P somatic mutation in Waldenström's macroglobulinemia

  NEJM

• 2012Myelodysplastic syndromes: revisiting the role of the bone marrow microenvironment in disease pathogenesis

  International Journal of Hematology

• 2012New concepts and best practices for management of pre- and post-transplantation cancer

  Transplantation Reviews

• 2012Novel Agents and Approaches for Advanced Renal Cell Carcinoma

  Journal of Urology

• 2012Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer (Study 19)

  NEJM

• 2012Oncolytic virotherapy

  Nature Biotechnology

  John C. Bell
• 2012Pazopanib for metastatic soft-tissue sarcoma (PALETTE)

  Lancet

• 2012Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative

  Clinical Cancer Research

• 2012Phase III trial of adjuvant capecitabine/cisplatin with or without radiotherapy in D2-resected gastric cancer (ARTIST)

  Journal of Clinical Oncology

• 2012Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer

  New England Journal of Medicine

• 2012Preoperative chemoradiotherapy for esophageal or junctional cancer (CROSS)

  NEJM

• 2012Randomized Phase II Trial of Everolimus in Combination With Tamoxifen in Patients With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negat...

  Journal of Clinical Oncology

• 2012Recurring founder mutations in BRCA1 and BRCA2 in ethnically diverse Jewish populations

  Breast Cancer Research and Treatment

• 2012Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 no...

  Lancet

• 2012Robotic Versus Laparoscopic Partial Nephrectomy for Complex Tumors: Comparison of Perioperative Outcomes

  European Urology

• 2012Safety, activity, and immune correlates of anti-PD-1 antibody in cancer

  New England Journal of Medicine

• 2012Sensing of cell death by myeloid C-type lectin receptors

  Current Opinion in Immunology

• 2012Strategies of radioiodine ablation in patients with low-risk thyroid cancer (ESTIMABL1)

  NEJM

• 2012Targeting Epigenetic Readers in Cancer

  New England Journal of Medicine

• 2012The blockade of immune checkpoints in cancer immunotherapy

  Nature Reviews Cancer

• 2012The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

  Proceedings of the National Academy of Sciences of the United States of America

• 2012The Crucial Role of Clinician Engagement in System-Wide Quality Improvement: The Cancer Care Ontario Experience

  Healthcare Quarterly

• 2012The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups (METABRIC)

  Nature

• 2012Treatment of older patients with mantle-cell lymphoma (MCL Elderly)

  NEJM

• 2012U.S. Food and Drug Administration Approval Summary: Brentuximab Vedotin for the Treatment of Relapsed Hodgkin Lymphoma or Relapsed Systemic Anaplastic Large-Cel...

  Clinical Cancer Research

• 2012Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR

  Nature

• 2012ΔNp63α represses anti-proliferative genes via H2A.Z deposition

  Genes & Development