Assessing Outcomes Emerging After Conversion to Regular Approval for Cancer Drug Indications Granted Accelerated Approval, 1992-2021.

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 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 remain 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.