{"entity":{"id":"paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020","kind":"paper","name":"Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC","aka":[],"tldr":"In the patients whose tumours showed the most PD-L1, immunotherapy alone gave a median survival of 20.2 months against 13.1 on chemotherapy, with far fewer severe side effects.","summary":"Herbst, Giaccone, de Marinis and colleagues randomised 572 patients with metastatic non-squamous or squamous non-small-cell lung cancer, untreated and with PD-L1 expression on at least 1 percent of tumour cells or tumour-infiltrating immune cells by the SP142 assay, 1 to 1 between atezolizumab and platinum-based chemotherapy. Overall survival was tested hierarchically by PD-L1 status among patients whose tumours were EGFR and ALK wild-type.\n\nIMpower110 is the trial that generalised KEYNOTE-024's result to a second drug and a second assay, and in doing so exposed the assay problem: SP142, 22C3 and SP263 score different things and select different patients, so PD-L1 high means different populations in different trials.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2020","url":"https://doi.org/10.1056/NEJMoa1917346"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32997907/"},{"label":"ClinicalTrials.gov NCT02409342","url":"https://clinicaltrials.gov/study/NCT02409342"}],"tags":["lung-evidence"],"related":["paper-keynote-024-nejm-2016","paper-keynote-042-lancet-2019","paper-keynote-001-pembrolizumab-nsclc-nejm-2015","immunotherapy-roadmap"],"cancers":["lung-cancer","nsclc","pdl1-high-nsclc"],"sections":["immunotherapy","diagnostics"],"technologies":["ihc","checkpoint-inhibitor"],"targets":["pd1"],"drugs":["atezolizumab","pembrolizumab","carboplatin","cisplatin"],"companies":["roche-genentech"],"institutions":[],"pathways":["immune-checkpoint"],"terms":["pdl1","tps","tmb"],"trials":[],"people":["roy-herbst"],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2020,"doi":"10.1056/NEJMoa1917346","pmid":"32997907","authors":"Herbst RS, Giaccone G, de Marinis F, et al.","paperType":"rct","findings":["In EGFR and ALK wild-type patients with the highest PD-L1 expression (205 patients), median overall survival was 20.2 months with atezolizumab against 13.1 months with chemotherapy: hazard ratio for death 0.59 (P equals 0.01).","Adverse events occurred in 90.2 percent of patients on atezolizumab and 94.7 percent on chemotherapy.","Grade 3 or 4 adverse events occurred in 30.1 percent on atezolizumab and 52.5 percent on chemotherapy.","Overall and progression-free survival favoured atezolizumab in the subgroups with high blood-based tumour mutational burden."],"whatItMeans":"For the minority of patients whose tumours express a lot of PD-L1, a single antibody outperforms chemotherapy and is far easier to take. The word minority is the point: the same drug in the same disease at lower PD-L1 gives much less.","caveats":["The headline result is in 205 of 572 enrolled patients, the highest PD-L1 subgroup within the wild-type population; the hierarchical testing stopped there.","SP142 is not interchangeable with the 22C3 assay used in the KEYNOTE trials, so eligibility does not transfer between them.","Blood-based tumour mutational burden was exploratory and has not become a routine selection tool."],"changedPractice":true,"participants":572},"route":"/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/","neighbours":{"paper":[{"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/"},{"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/"},{"id":"paper-keynote-042-lancet-2019","kind":"paper","name":"Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial","route":"/key-papers/paper-keynote-042-lancet-2019/"},{"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/"}],"roadmap":[{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"},{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}],"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pdl1-high-nsclc","kind":"cancer","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","route":"/cancers/pdl1-high-nsclc/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"term":[{"id":"immune-checkpoint","kind":"term","name":"Immune checkpoint","route":"/terms/immune-checkpoint/"},{"id":"ihc","kind":"term","name":"Immunohistochemistry (IHC)","route":"/terms/ihc/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"},{"id":"tps","kind":"term","name":"Tumour proportion score (TPS)","route":"/terms/tps/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"person":[{"id":"roy-herbst","kind":"person","name":"Roy S. Herbst","route":"/people/roy-herbst/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}