Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval (2024)

• ¹Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts

Key Points

Question What is the clinical benefit of cancer drugs granted accelerated approval, and on what basis are they converted to regular approval?

Findings In this cohort study of cancer drugs granted accelerated approval from 2013 to 2017, 41% (19/46) did not improve overall survival or quality of life in confirmatory trials after more than 5 years of follow-up, with results not yet available for another 15% (7/46). Among drugs converted to regular approval, 60% (29/48) of conversions relied on surrogate measures.

Meaning Although accelerated approval can be useful, some cancer drugs do not end up demonstrating benefit in extending patients’ lives or improving their quality of life.

Importance The US Food and Drug Administration’s (FDA) accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered “reasonably likely” to predict clinical benefit. Postapproval clinical trials are then required to confirm whether these drugs offer clinical benefit.

Objective To determine whether cancer drugs granted accelerated approval ultimately demonstrate clinical benefit and to evaluate the basis of conversion to regular approval.

Design, Setting, and Participants In this cohort study, publicly available FDA data were used to identify cancer drugs granted accelerated approval from 2013 to 2023.

Main Outcomes and Measures Demonstrated improvement in quality of life or overall survival in accelerated approvals with more than 5 years of follow-up, as well as confirmatory trial end points and time to conversion for drug-indication pairs converted to regular approval.

Results A total of 129 cancer drug–indication pairs were granted accelerated approval from 2013 to 2023. Among 46 indications with more than 5 years of follow-up (approved 2013-2017), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and 7 (15%) remained ongoing after a median of 6.3 years. Fewer than half (20/46, 43%) demonstrated a clinical benefit in confirmatory trials. Time to withdrawal decreased from 9.9 years to 3.6 years, and time to regular approval increased from 1.6 years to 3.6 years. Among 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival, 21 (44%) on progression-free survival, 5 (10%) on response rate plus duration of response, 2 (4%) on response rate, and 1 (2%) despite a negative confirmatory trial. Comparing accelerated and regular approval indications, 18 of 48 (38%) were unchanged, while 30 of 48 (63%) had different indications (eg, earlier line of therapy).

Conclusions and Relevance Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes.

Oncology Drug Development Law and Medicine

Citation

Liu ITT, Kesselheim AS, Cliff ERS. Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval. JAMA. Published online April 07, 2024. doi:10.1001/jama.2024.2396

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