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Overall survival (OS) is how long patients live, full stop. It is the gold-standard endpoint.
Overall survival (OS) is the time from random assignment to death from any cause, and it remains the gold-standard endpoint in oncology trials. Its interpretation is confounded by crossover and by therapies given after progression, and it requires long follow-up. Regulators increasingly want to see that OS is not harmed even when PFS is the primary endpoint. The term is cited by the Small-cell lung cancer and Hodgkin lymphoma entries, the ZUMA-7 trial and Michael LeBlanc, and it runs through the bottlenecks on trial design, weak real-world evidence, patient voice and quality of life. Related ideas include randomising the next line of treatment before the first fails, a regulatory endpoint for antimetastatic drugs and seamless phase 2/3 trials with pre-registered go rules.
The 48 most recent of 71 papers; see them all →
The survival benefit first reported in 2023 has held five years after the last dose of adjuvant osimertinib, which answers the worry that a three-year course only delays relapse. Patients with an exon 19 deletion gained most; the L858R estimate crosses one and is less certain. Nothing here changes the recommendation, which already rests on the 2023 analysis, but it tightens the case for testing every resected non-squamous tumour for EGFR mutations.
The latest in a line of negative targeted-therapy trials in triple-negative disease (EGFR, VEGF, iniparib, now AKT): a modest delay in progression that did not translate into survival, in the same year that an antibody-drug conjugate did. It is why the roadmap treats pathway-targeted small molecules as the road not taken.
The first-line overall survival result that made an antibody-drug conjugate the standard for PD-L1-negative or immunotherapy-ineligible metastatic triple-negative disease, and the reason the sequencing question (which TROP2 drug first, what after it) is now urgent.
Answers the two questions that hung over adjuvant olaparib, durability and late leukaemia, in its favour; the remaining question is whether carriers who also received pembrolizumab or capecitabine, whom the trial did not study, get the same benefit.
Chinese patients in the trial saw the same pattern as the global population: a clear progression-free survival gain, no proven survival gain, and a different rather than heavier side-effect burden, with mouth and eye toxicity in nearly half. It supports use of datopotamab deruxtecan in this setting in China but does not resolve the global trial's missing survival benefit.
Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.
For patients with advanced melanoma, immunotherapy offers a realistic chance of long-term survival and probably cure, and the ten-year data show that patients who are alive and progression-free at three years rarely die of melanoma afterwards. Nivolumab plus ipilimumab gives the best long-term results but at a high price in serious side effects; nivolumab alone or nivolumab plus relatlimab are alternatives for patients at lower risk or with autoimmune concerns. The trial is also a caution about surrogate endpoints: the survival plateau took years to become visible.
The tail of long survivors is the case for chemo-immunotherapy in gallbladder cancer, where the median gain is under two months. Who lands in that tail is still unknown; no biomarker in the trial predicts it.
Shares Slamon 2001: adding trastuzumab to chemotherapy for HER2-positive metastatic breast cancer, CheckMate 057: nivolumab beats docetaxel after chemotherapy in non-squamous lung cancer, An independent programme that validates surrogate endpoints, setting by setting, KEYNOTE-006 (Robert 2015): pembrolizumab versus ipilimumab in advanced melanoma.
Shares NAPOLI-3: NALIRIFOX versus gemcitabine plus nab-paclitaxel as first treatment for metastatic pancreatic cancer, RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma, RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer, CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer.
Shares Cheap long-term survival follow-up by linking trial participants to registries, Every patient on an accelerated-approval drug enrolled in a registry until confirmation, Provisional prices for surrogate-endpoint approvals, reset when survival data arrive, Patent term extension scaled to proven survival gain.
Shares Provisional prices for surrogate-endpoint approvals, reset when survival data arrive, Launch prices indexed to the ESMO benefit scale, revisited when survival matures, Power trials to detect a benefit patients would value, not the smallest detectable one, Pharmaceutical Benefits Advisory Committee.
Shares RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma, RUBY: dostarlimab with chemotherapy for advanced or recurrent endometrial cancer, Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma, HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer.
Shares Stupp 2005: temozolomide added to radiotherapy for newly diagnosed glioblastoma, NAPOLI-3: NALIRIFOX versus gemcitabine plus nab-paclitaxel as first treatment for metastatic pancreatic cancer, IMbrave150: atezolizumab plus bevacizumab replaces sorafenib as first treatment for advanced liver cancer, KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival).
Shares ADMIRAL: gilteritinib pills versus chemotherapy for relapsed FLT3-mutated acute myeloid leukaemia, AGILE: ivosidenib plus azacitidine for newly diagnosed IDH1-mutated AML in patients unfit for intensive chemotherapy, INO-VATE: inotuzumab ozogamicin, a CD22 antibody-drug conjugate, versus chemotherapy for relapsed adult B-cell ALL, IRIS: imatinib versus interferon plus cytarabine as first treatment for chronic myeloid leukaemia.
Shares Median survival, Reading a hazard ratio, Absolute versus relative benefit (number needed to treat), Endpoint.