Study: Certain cancer drugs saw widespread use before accelerated approval withdrawal

In the period between when three accelerated approval (AA) drugs received approval from the US Food and Drug Administration (FDA) for oncology indications and were later withdrawn due to negative confirmatory trials, more than one quarter of patients with breast, bladder, hepatocellular, gastric, or small cell lung cancer received an AA drug rather than standard of care, according to a research letter recently published in JAMA Oncology.

“Given the growth of withdrawals due to negative confirmatory trials and emerging evidence on the high spending associated with AA drugs, it is critical to balance early access against population-level exposure to cancer therapies with no benefit over standard of care,” Ravi Parikh, MD, MPP, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues wrote in their study.

Using data from electronic health record (EHR)-derived de-identified databases, Dr. Parikh and colleagues performed a cross-sectional study evaluating 4,342 patients with advanced or recurrent breast, bladder, hepatocellular, gastric or small cell lung cancer between May 2016 and March 2022 who underwent treatment initiation with one of three drugs that had five oncology indications.

The patients received at least one line of an oncology systemic therapy that was approved by the FDA through the accelerated approval pathway and was later withdrawn after a negative phase 3 confirmatory trial. Patients in the study were median 70 years old, 61% were men, 67% were white, and 85% received treatment at a community practice. In total, 6,560 lines of therapy across five disease-specific indications were studied. The drugs evaluated included Tecentriq (atezolizumab) for triple-negative breast cancer and bladder cancer, Keytruda (pembrolizumab) for PD-L1 positive gastric cancer, and Opdivo (nivolumab) for hepatocellular cancer and small cell lung cancer.

A median of 46 months elapsed between approval and withdrawal, the researchers said. During that time, oncology drugs that were later withdrawn were used in 1,361 treatment initiations (26.1%), including 23.1% in triple-negative breast cancer, 22.5% in bladder cancer, 38.8% in hepatocellular cancer, 41.4% in gastric cancer and 23.6% in small cell lung cancer.

Clinicians were more likely to initiate treatment using one of these AA drugs between approval and publication of a confirmatory trial with negative results compared to the time between negative trial publication and withdrawal (35.5% vs. 15.7%). Specifically, use of oncology drugs for treatment initiation were higher prior to negative trial publication compared to after publication in patients with triple-negative breast cancer (24.1% vs. 8.6%), bladder cancer (39.7% vs. 12.8%), hepatocellular cancer (55.6% vs. 20.3%), gastric cancer (71.4% vs. 38.6%), and small cell lung cancer (21.0% vs. 2.5%).

The researchers said their analysis was limited by not being able to examine population-level exposure due to insufficient sample and follow-up being available for only 5 withdrawn AA indications.

“Earlier access and more rapid FDA responses to negative confirmatory trial data, a key proposal of the Accelerated Approval Integrity Act proposed in March 2022, may minimize exposure to AA therapies with lack of benefit,” Dr. Parikh and colleagues concluded.

JAMA Oncol Parikh et al.

Study: Certain cancer drugs saw widespread use before accelerated approval withdrawal

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