Study finds use of cancer medications declines after withdrawal of accelerated approval

Cancer medications that had their accelerated approval indications withdrawn by the US Food and Drug Administration (FDA), but were still on the market for another approved indication saw a decline in their use following a negative confirmatory trial result, according to a recent research letter published in JAMA Oncology.

“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,” Catherine S. Hwang, of the division of pharmacoepidemiology and pharmacoeconomics in the department of medicine at Brigham and Women’s Hospital in Boston, and colleagues wrote in their study.

“In some cases, there were substantial delays between accelerated approval, publicization of the negative trial results, and formal withdrawal of the indication from FDA-approved labeling.

Hwang and colleagues examined the usage patterns of four cancer medications granted accelerated approval for 762,752 patients—atezolizumab for breast cancer, atezolizumab for urothelial cancer indications, idelalisib for follicular lymphoma, and romidepsin for peripheral T-cell lymphoma—that had their accelerated approval status withdrawn after the results of their respective confirmatory trials but stayed on the market due to other indications. The drugs were granted accelerated approval and received published negative trial results between 12 months and 113 months, and the time it took to withdraw the drug from accelerated approval was between 1 month and 47 months.

The researchers found the monthly medication use increased for idelalisib (52 per million patients; 95% CI, 27-77), romidepsin (86 per million patients; 95% CI, 59-112), and atezolizumab for the breast cancer indication (16 per million patients; 95% CI, 12-21) prior to the publication of negative trial results or an FDA safety warning. Following the accelerated approval withdrawal, idelalisib use decreased by 63 per million patients (95% CI, -89 to -37), romidepsin use decreased by 344 per million patients (95% CI, -611 to -77), and atezolizumab for breast cancer decreased by 28 per million patients (95% CI, -35 to -20).

One reason why usage decreased may be because of rapid incorporation of data into practice on the part of oncologists, or because there was a payer restriction on coverage of ineffective drugs. In other cases, drug usage was reduced but did not go down to zero. In the case of romidepsin, usage is likely to continue because “the confirmatory trial was conducted in a heterogeneous population, in which there was some evidence of efficacy in patients with certain subtypes of peripheral T-cell lymphoma,” Hwang and colleagues said

Researchers noted several limitations in their study, such as the small sample size for medication use, focus on a population of commercially insured patients, and not being able to isolate regulatory events from other events that could potentially impact usage.

“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,” Hwang and colleagues concluded.

JAMA Oncol Hwang et al.

Study finds use of cancer medications declines after withdrawal of accelerated approval

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