OBR OncologyDoes FDA Withdrawal of Cancer Drug Show Bigger Changes Needed?

Evaluating the Impact of Accelerated Drug Approvals on Oncology Care

The US Food and Drug Administration’s (FDA’s) accelerated approval policy is designed to provide rapid access to promising cancer drugs, but recent withdrawals highlight the need for more robust evidence in the approval process. This article examines the case of melphalan flufenamide’s withdrawal and the broader implications for oncology drug development, emphasizing the importance of stringent clinical trial design and the balance between innovation and patient safety.

Key Points:

• The FDA’s accelerated approval policy aims to quickly deliver promising drugs to patients with serious diseases, using interim markers of benefit instead of direct improvements in overall survival.
• Mikkael A. Sekeres, MD, emphasizes the necessity of follow-up trials to confirm the benefits observed in initial studies leading to accelerated approvals.
• Critics, including Simone N. Koole, MD, PhD, argue for approvals based on more rigorous evidence, ideally from randomized controlled trials (RCTs), to prevent bias and ensure treatment efficacy.
• The Lancet Oncology published a policy review advocating for stricter standards in the approval process, highlighting the withdrawal of several oncology drugs post-accelerated approval due to lack of confirmed benefits or safety issues.
• The withdrawal of melphalan flufenamide (Pepaxto) underscores the risks associated with accelerated approvals, as subsequent trials showed potential increased risk of death and significant toxicity.
• Dr. Sekeres advocates for cancer drugs to demonstrate improvements in overall survival, with progression-free survival alone deemed insufficient in the absence of quality of life improvements.
• There is a call for alignment between the FDA and the European Medicines Agency (EMA) regarding standards for accelerated approvals and drug re-evaluation processes.
• The role of clinicians in the Netherlands highlights the need for robust data on long-term efficacy and safety, as current accelerated approval processes may lack comprehensive information.

“All cancer drugs should demonstrate that they improve survival compared to previous standards…I would argue that ideally, drugs should demonstrate improvements in overall survival, and that progression-free survival, in the absence of improvement in quality of life, is not enough.”
– Dr. Mikkael A. Sekeres, Chief of the Division of Hematology in the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine

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