In 2018, there were sharp upticks in PD-L1 testing and the use of chemotherapy for the treatment of urothelial carcinoma (UC), coupled with a large drop in the use of immunotherapies (including pembrolizumab, atezolizumab, nivolumab, avelumab, and durvalumab) for this condition, according to researchers from the Flatiron Health, the US Food and Drug Administration (FDA), the University of Pennsylvania, and the Icahn School of Medicine at Mount Sinai.1

These changes coincided with developing information from the phase 3 KEYNOTE-361 ( Identifier: NCT02853305) and the IMvigor130 ( Identifier: NCT02807636) trials, which revealed that cisplatin-sensitive patients with disease characterized by low PD-L1 expression who were treated with the immunomodulators atezolizumab or pembrolizumab had poorer overall survival (OS).

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The investigators asserted that the FDA’s effective communication2 in and around June 2018 about immunotherapy label restrictions was associated with the changes seen in clinical prescribing habits of immunotherapies. They observed that the use of chemotherapy for UC increased from January 2016 to January 2019, and the use of immunotherapies decreased after the FDA restricted first-line atezolizumab and pembrolizumab use to include only those patients whose tumors expressed PD-L1.1

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In their research letter published in JAMA, Ravi B. Parikh, MD, of the University of Pennsylvania in Philadelphia, and colleagues attributed the drop in immunotherapy prescriptions for patients with UC as likely evidence that the safety message originating from the FDA was successfully amplified — and that oncologists reacted to the update swiftly to create actionable change. Some questions remained, however, regarding how many oncologists ultimately received those regulatory updates and if the messages on the FDA’s newly narrowed indications were truly what prompted physicians to alter their prescribing practices.

Cancer Therapy Advisor asked Dr Parikh about how the FDA confirmed that its communication efforts were indeed received by the intended audience. Of note, one of the study coauthors is Sean Khozin, MD, MPH, who is the acting associate director in the FDA’s Oncology Center of Excellence.

When Dr Parikh was asked about other factors outside of FDA alerts that could have influenced the administration of PD-1/PD-L1 inhibitors in UC, he acknowledged that his team did not account for drug cost to patients or potential formulary changes when they made these conclusions — but he told Cancer Therapy Advisor that the investigators on the project still “felt that is was unlikely that these changes would occur across our entire population at the same time.”