Label Restrictions After Accelerated Approval Impacts Use, Researchers Find
Researchers have found an association between a labeling restriction placed on two immunotherapy drugs, which initially won accelerated approval, and a decrease in their use, according to an article appearing in JAMA last week.In 2017, the US Food and Drug Administration (FDA) granted accelerated approval to Merck's Keytruda (pembrolizumab) and Roche's Tecentriq (atezolizumab) for first-line use to treat bladder cancer in patients who are ineligible for cisplatin-based chemotherapy regardless of programmed death ligand 1 (PD-L1) expression based on single open-label, single-arm Phase II studies.
However, in 2018, FDA limited the use of both drugs after data from ongoing studies showed that patients with low PD-L1 expression had decreased survival taking either drug as monotherapy compared to platinum-based chemotherapy.
Specifically, FDA indicated that the drugs should only be used in patients whose PD-L1 expression meets a certain threshold, which left the door open to both drugs' use in patients who are not eligible for any platinum-based chemotherapy.
"FDA's decision to restrict the indication after accelerated approval based on early review of confirmatory trial data was unique," the authors write, noting that the move’s impact on clinical practice was unclear at the time.
To determine the impact of the label restrictions, the authors looked at the first-line treatments for nearly 2000 patients diagnosed with advanced bladder cancer from 2016 to 2019 and whether the patients were tested for PD-L1 expression.
One-third of the patients received first-line immunotherapy while more than half (58%) were started on chemotherapy. Following FDA's move to alter the labels for Keytruda and Tecentriq, the authors observed a decrease in the use of immunotherapy compared to chemotherapy. The authors also found that PD-L1 testing increased by more than double in a year.
"Given the rapid growth of oncology therapies receiving accelerated approval, how regulatory responses to postmarket safety events affect the use of such drugs is important," the authors write.
While the authors say their findings suggest that clinical practice changed in response to the labeling changes, they note that "limitations include that clinician adherence to the revised label change could not be determined" and that the impact on patients' outcomes requires additional study.
JAMA