Oncologists Responsive to FDA Label Restrictions

After the FDA restricted the labels of 2 drugs used to treat bladder cancer, oncologists' use of these treatments decreased drastically.

Findings of a new study1 published in JAMA Network show that oncologists’ use of 2 drugs restricted by the US Food and Drug Administration (FDA) decreased by about half within 6 months of the restriction. 

The 2 drugs, pembrolizumab (Keytruda) and atezolizumab (Tecentriq), were first granted accelerated approval for bladder cancer based on the results of a single-group phase 2 study in patients who were ineligible for first-line treatment with cisplatin-based chemotherapy. However, ongoing data from phase 3 trials has shown patients with PD-L1 negative tumors assigned to immunotherapy are seeing worse outcomes compared with platinum-based chemotherapy. Based on these data, the FDA limited the indication for the 2 immunotherapies to cisplatin-ineligible patients with PD-L1 positive tumors. 

“We felt it was important to evaluate what the data says about this program, and our findings show oncologists are quick to respond to emerging safety data for drugs approved through this process,” the study’s senior author Ronac Mamtani, MD, MSCE, an assistant professor of hematology-oncology in the Perelman School of Medicine at the University of Pennsylvaniasaid in a press release.

Researchers from the University of Pennsylvania analyzed data from the Flatiron Health database from 1965 patients diagnosed with advanced bladder cancer between January 2016 and January 2019 who were treated with at least one line of systemic therapy. They looked at usage rates of immunotherapy among these patients; 645 initiated first-line immunotherapy and 1147 initiated first-line chemotherapy. 

According to the results, the label change was associated with decreased immunotherapy use and an increase in PD-L1 testing. From May 2018 to January 2019, the unadjusted rate of immunotherapy decreased from 51.9 per 100 patients to 30.3 per 100 patients. The rate of chemotherapy during the same period increased from 37.0 per 100 patients to 60.6 per 100 patients. The rate of PD-L1 testing more than doubled from 9.3 per 100 patients to 21.2 per 100 patients. 

“Given the rapid growth of oncology therapies receiving accelerated approval, how regulatory responses to post-market safety events affect use of such drugs is important,” the researchers wrote.“This study suggests that the FDA label changes were associated with changes in practice, even when the decision was based on emerging trial data.”


The researchers noted that the study could not analyze clinicians’ adherence to the revised label change or the effect of the label change on clinical outcomes. 


Parikh RB, Adamson BJS, Khozin S, et al. Association Between FDA Label Restriction and Immunotherapy and Chemotherapy Use in Bladder Cancer. JAMA. 2019;322(12):1209–1211. doi:10.1001/jama.2019.10650