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

Abstract

(Neo)adjuvant systemic treatments aim to improve overall survival (OS)_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 (QOL). We examine the design, reporting, and outcomes of Food and Drug Administration (FDA)-approved drugs for solid tumors. We searched FDA (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. Twenty-four studies supporting 25 approvals met inclusion criteria. Common tumor types included melanoma (7/24, 29%), breast (6/24, 25%) and non-small cell lung cancer (6/24, 25%). Among 21 trials reporting OS, 52% (11/21) showed benefit at any time, but only 36% (4/11) reported OS benefits at the time of approval and/or primary publication. In 21 trials (88%) the expected number of events could be reproduced, in 11 trials (46%) 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. QOL outcomes were reported in 79%, with 31% reported clinically meaningful declines in one or more domains. (Neo)adjuvant trials often lack transparency in sample size justifications and censoring rules. Approximately half demonstrated an OS improvement at any time, and one third showed a decline in QOL. Greater standardization in trial designs and reporting is needed to ensure trials align with patient and healthcare priorities.