FDA Grants Full Approval to Pembrolizumab for Select Locally Advanced or Metastatic Urothelial Cancer

The FDA has granted a full approval to pembrolizumab (Keytruda) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for any platinum-containing chemotherapy.¹

The regulatory agency announced a label update for the immunotherapy, regarding its indication in frontline advanced urothelial carcinoma in the United States. Specifically, the agency converted this indication from an accelerated approval to a full approval, and has revised the label for those with locally advanced or metastatic urothelial carcinoma who are ineligible for platinum-containing chemotherapy.

Previously, pembrolizumab was indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who were not candidates to receive cisplatin-containing chemotherapy and whose tumors had a PD-L1 expression of a combined positive score (CPS) of 10 or higher, per an FDA-approved test, or in those who were not eligible to receive any platinum-containing chemotherapy irrespective of PD-L1 status.

This indication had been given the green light under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication was dependent upon verification and description of clinical benefit in confirmatory trials.

In the phase 3 KEYNOTE-361 trial (NCT02853305), investigators evaluated pembrolizumab as a single agent and in combination with chemotherapy for use in the frontline treatment of patients with advanced or metastatic urothelial carcinoma who were candidates to receive platinum-containing chemotherapy. The trial did not meet its prespecified dual primary end points of overall survival or progression-free survival, vs standard-of-care chemotherapy.

Previously, in April 2021, the FDA's Oncologic Drugs Advisory Committee voted 5 to 3 to uphold the accelerated approval of pembrolizumab in the first-line treatment of patients with cisplatin-ineligible and carboplatin-ineligible locally advanced or metastatic urothelial carcinoma.²

“While the treatment landscape has evolved, an unmet need remains for appropriate patients newly diagnosed with certain types of advanced urothelial carcinoma who are not eligible for platinum-containing chemotherapy,” Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, stated in a press release. “We are confident in the role [pembrolizumab] will continue to play for these patients who have few other treatment options and are working with urgency to advance studies to help more patients living with bladder and other types of cancer.”

References

1. FDA approves updated indication for Merck's KEYTRUDA (pembrolizumab) for the treatment of certain patients with urothelial carcinoma (bladder cancer). News release. Merck. August 31, 2021. Accessed August 31, 2021. https://bwnews.pr/3zCgh3N
2. Oncologic Drugs Advisory Committee (ODAC) Meeting. FDA. April 28, 2021. Accessed August 31, 2021. https://collaboration.fda.gov/ODAC04282021?disclaimer-consent=true&proto=true.