Assessing outcomes emerging after conversion to regular approval for cancer drug indications granted accelerated approval, 1992-2021

Tibau, A; Romano, A; Liu, ITT; Han, J; Cliff, ERS; Kesselheim, AS

Author(s): Tibau, A; Romano, A; Liu, ITT; Han, J; Cliff, ERS; Kesselheim, AS;
Details: Publication Year 2025-10-01,Volume 117,Issue #10,Page 2103-2111
Journal Title: Journal of the National Cancer Institute
Publication Type: Research article
Abstract: BACKGROUND: The FDA's accelerated approval pathway expedites cancer drug approvals based on surrogate measures, while clinical benefit is assessed in post-approval confirmatory trials. Many confirmatory trials also rely on surrogate measures rather than overall survival (OS) or quality of life (QoL). We evaluated how often accelerated approvals demonstrate clinical benefits at the time of conversion to regular approval, and if not, how often OS, QoL, or substantial clinical benefit emerge post-conversion. METHODS: This retrospective cohort study reviewed FDA cancer drug accelerated approvals converted to regular approval (1992-2021), with follow-up through December 2024. We assessed confirmatory trial endpoints (OS and QoL) at conversion and searched for updated evidence post-conversion. Clinical relevance was assessed using the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS). RESULTS: Of 77 confirmatory trials, 25 (32%) showed OS benefit at conversion; 52 (68%) relied on surrogate measures. After a median 5-year follow-up, OS benefit emerged for 7 (9%) additional indications. QoL benefit was shown in 9 (12%) confirmatory trials at conversion and in 4 (5%) post-conversion. Among 73 (95%) confirmatory trials scoreable by ESMO-MCBS, 34 (47%) met the substantial clinical benefit threshold at conversion. Of the 31 (97%) trials with a survival benefit evaluable by ESMO-MCBS, 19 of 24 (79%) met the threshold at conversion and 5 of 7 (71%) post-conversion. CONCLUSIONS: Once oncology drugs are converted from accelerated to full approval, new evidence of OS or QoL gains remains rare, underscoring the need to ensure such evidence is available at conversion. Patients should be informed of evidence variability, and the ESMO-MCBS can provide valuable guidance.
Publisher: Oxford University Press
Keywords: Humans; *Drug Approval; United States; *Antineoplastic Agents/therapeutic use; Quality of Life; United States Food and Drug Administration; *Neoplasms/drug therapy/mortality; Retrospective Studies; Treatment Outcome; Clinical Trials as Topic
Department(s): Haematology
Publisher's Version: https://doi.org/10.1093/jnci/djaf195
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-08-28 11:09:25

Last Modified: 2025-11-25 12:06:36