Overall survival in oncology phase III trials: an individual patient level meta-analysis (OPTIMA)

Designing phase III oncology trials to demonstrate overall survival (OS) superiority may be challenging due to sample size, follow-up time, resources, and costs as compared to trials evaluating intermediate endpoints, which may or may not be reliable surrogates of OS. In this study, we investigate at scale the relative gains in OS achieved in modern phase III oncology trials using OS primary endpoints in OPTIMA, a prospectively registered, pre-specified meta-analysis leveraging a large assembly of reconstructed individual patient-level data (PROSPERO: CRD420251162778). After screening 1184 trials and excluding 937 without an OS primary endpoint, 159 trials enrolling 104 740 patients met the inclusion criteria. In the two-stage Cox model, randomization to the experimental arm was associated with improvement in OS (random effects HR, 0.87; 95% CI, 0.85–0.89; P < .0001). In the one-stage Cox model stratified by trial identity, OS was also longer with the experimental arm (HR, 0.88; 95% CI, 0.85–0.90; P < .0001). Taken together, the data from OPTIMA should encourage renewed enthusiasm among trialists, funders, regulatory agencies, and policymakers for prioritizing phase III oncology trials evaluating OS primary endpoints. © The Author(s) 2026. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.