Cancer Drug Use Declines After Negative Confirmatory Trials

TOPLINE:

The use of cancer drugs with withdrawn US Food and Drug Administration (FDA) accelerated approval indications declined significantly after publication of negative confirmatory trials, despite the drugs remaining available for off-label use, a cohort study found.

METHODOLOGY:

• The FDA’s accelerated approval program allows drugs for serious conditions to enter the market based on preliminary evidence, with confirmatory trials required postapproval. If these trials fail to confirm clinical benefit, indications may be withdrawn.
• Researchers identified three cancer drugs that had withdrawn accelerated approval indications between January 2020 to December 2022 but remained on the market for at least one other indication: Atezolizumab for breast cancer and two urothelial cancer indications, idelalisib for follicular lymphoma, and romidepsin for peripheral T-cell lymphoma.
• Using a national commercial claims database, the researchers created four cohorts of patients who had the withdrawn indications. The study included 762,752 patients.
• Researchers evaluated changes in the monthly proportion of new (no use in the prior 365 days) and ongoing medication use after the first public reporting of negative trial results or FDA safety warning.

TAKEAWAY:

• The time between accelerated approval and first publicized negative trial results ranged from 12 to 113 months, with regulatory withdrawal occurring 1-47 months after trial results were reported.
• Among patients with breast cancer, the monthly use of atezolizumab increased by 16 per million patients before the publication of negative trial results, decreased by 28 per million patients after the publication of results and continued to decline over time.
• Among patients with follicular lymphoma, the use of idelalisib increased by 52 per million patients before the FDA issued a safety warning and decreased by 63 per million patients after, and also continued to decline over time.
• Romidepsin continued to be used for its withdrawn indication because of some evidence of efficacy in patients with certain subtypes of peripheral T-cell lymphoma, despite the confirmatory trial being conducted in a heterogeneous population.

IN PRACTICE:

“The use of the oncology medications we studied responded quickly to cautionary signals and decreased after confirmatory trials that failed to demonstrate efficacy, despite their ongoing availability via off-label prescribing,” the authors wrote. “Ensuring timely completion of postapproval studies and enforcing appropriate regulatory actions based on negative trial results is necessary to minimize patient exposure to ineffective and potentially unsafe medications.”

SOURCE:

This study, led by Catherine S. Hwang, MD, MSPH, Division of General Internal Medicine and Geriatrics, Oregon Health & Science University in Portland, Oregon, was published online in JAMA Oncology.

LIMITATIONS:

This study focused on a commercially insured population and could not isolate the effects of regulatory events from other factors such as the approval of alternative therapies. Additionally, this study was underpowered to detect significant changes in medication use owing to the small sample size.

DISCLOSURES:

This study was funded by a grant from Arnold Ventures and the Commonwealth Fund to Brigham and Women’s Hospital, Boston. Two authors reported receiving grants from The Elevance Health Public Policy Institute and The National Academy for State Health Policy and personal fees from Alosa Health, outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.