(Neo)adjuvant approvals for solid tumors by the US Food and Drug Administration 2010-2023

Abstract

Abstract Background (Neo)adjuvant systemic treatments aim to improve overall survival by reducing recurrence risk; however, there can be challenges, such as reliance on surrogate endpoints, censoring, loss to follow-up, and impact on quality of life. We examine the design, reporting, and outcomes of US Food and Drug Administration–approved drugs for solid tumors. Methods We searched Food and Drug Administration (neo)adjuvant approvals for solid tumors 2010-2023 with time-to-event endpoints. Trial characteristics, endpoints, and censoring were evaluated descriptively. Statistical designs and sample size calculations were assessed for reproducibility and transparency. Results A total of 24 studies supporting 25 approvals met inclusion criteria. Common tumor types included melanoma (7 of 24, 29%), breast (6 of 24, 25%), and non-small cell lung cancer (6 of 24, 25%). Among 21 trials reporting overall survival, 52% (11 of 21) showed benefit at any time, but only 36% (4 of 11) reported overall survival benefits at the time of approval and/or primary publication. In 21 (88%) trials the expected number of events could be reproduced, in 11 (46%) trials sample size calculations could be attempted (though calculations often differed), and only 14 (58%) stated expected absolute numerical outcomes. Censoring rules were applied inconsistently; only 36% defined rules adequately. Quality-of-life outcomes were reported in 79%, with 31% reporting clinically meaningful declines in one or more domains. Conclusions (Neo)adjuvant trials often lack transparency in sample size justifications and censoring rules. Approximately half demonstrated an overall survival improvement at any time, and one-third showed a decline in quality of life. Greater standardization in trial designs and reporting is needed to ensure trials align with patient and health-care priorities.