Maturity and Longitudinal Evolution of Overall Survival Evidence in Regular FDA Oncology Approvals, 2006–2025

Background: Regular FDA approval is presumed to reflect robust survival evidence for oncology drugs, yet the maturity, statistical significance, and clinical meaningfulness of overall survival (OS) evidence at authorization—and its evolution over time—remain poorly characterized.<br><br>Methods:&nbsp;We retrospectively identified regular FDA oncology approvals (January 2006–September 2025) from Drugs@FDA, restricted to indications supported by phase&nbsp;Ⅱ/Ⅲ&nbsp;randomized controlled trials (RCTs) with prespecified OS endpoints, with pivotal trial reports retrieved from MEDLINE, ClinicalTrials.gov, and Google Scholar. OS maturity at approval was quantified using&nbsp;information fraction (IF); clinical meaningfulness was assessed with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale. Outcomes included OS significance, clinical meaningfulness, and hazard ratio (HR) magnitude at approval and final update.<br><br>Findings: We included 258 regular approvals supported by 253&nbsp;RCTs; 207 (80.2%) were authorized on interim or immature OS data (median IF, 0.67; IQR, 0.48–0.99). At approval, 117 (45.4%) showed statistically significant OS benefit and 66 (25.6%) were clinically meaningful. Updated OS became available for 194 approvals: 35 (19.6%) converted from non-significant to significant versus 5 (2.8%) reversing, and 26 (14.4%) became clinically meaningful versus 7 (3.9%) losing meaningfulness. Conversely, HR magnitude attenuated slightly (median final-to-approval&nbsp;HR-ratio, 1.027; p&lt;0.001). Higher IF was associated with greater odds of OS significance (odds ratio [OR] 1.75, 95% CI 1.46–2.11) and clinical meaningfulness (OR 1.21, 1.05–1.38) at approval.<br><br>Interpretation: Regular FDA oncology approvals are frequently granted on interim or immature OS evidence, and statistical significance does not necessarily reflect clinically meaningful benefit. Greater attention to OS maturity, longitudinal evidence updating, and clinical meaningfulness, including quantitative metrics such as IF, is needed in regulatory and post-approval decision-making.Funding&nbsp;National Natural Science Foundation of China