FDA Converts Indication for Pembrolizumab as Frontline Therapy for Bladder Cancer to Full Approval


The FDA has granted a full approval to pembrolizumab for the treatment of platinum-ineligible patients with urothelial cancer.

An accelerated approval for pembrolizumab (Keytruda) as therapy for patients with locally advanced or metastatic urothelial cancer who are not eligible to receive platinum-based therapies has been converted to full approval following meetings with the FDA’s Oncologic Drugs Advisory Committee (ODAC), reported the drug’s developer, Merck.1

As part of an industry-wide effort by the FDA to reassess the status of systemic therapy agents granted accelerated approval and whose confirmatory trials did not denote a clinical benefit to treatment, this indication for pembrolizumab was reviewed with the ODAC, who voted 5 to 3 in favor of maintaining the accelerated approval despite disappointing findings in a phase 3 trial.

“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 for clinical research at Merck Research Laboratories, said in a press release. “We are confident in the role Keytruda 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.”

Results of the confirmatory phase 3 KEYNOTE-361 trial (NCT02853305) evaluating pembrolizumab in combination with chemotherapy vs standard-of-care chemotherapy alone for the first-line treatment of patients with advanced or metastatic urothelial carcinoma were reported in June 2020. The findings indicated that the pre-specified dual primary end points of overall survival (OS) or progression-free survival (PFS) were not meet.

Although there was an improvement in both end points in the final analysis (median follow-up, 31.7 months; interquartile range [IQR], 27.7-36.0) for patients treated with the anti–PD-1 therapy in combination with chemotherapy, these results did not meet statistical significance per the pre-specified statistical plan.

In the overall population, median PFS for the pembrolizumab arm was 8.3 months versus 7.1 months with chemotherapy alone, leading to a reduction in the risk of disease recurrence or death of 22% (HR, 0.78; 95% CI, 0.65-0.93; P = .0033). Similarly, the median OS was similar between the 2 arms at 17.0 months and 14.3 months, respectively (HR, 0.86; 95% CI, 0.72-1.02; P = .0407).2

In patients with a PD-L1 combined positive score of 10 or more, there was no benefit in the median OS between the pembrolizumab and control arms at 16.1 months versus 15.2 months, respectively (HR, 1.01; 95% CI, 0.77-1.32).

As part of its numerous indications, pembrolizumab is also approved as frontline maintenance therapy for patients with urothelial carcinoma following or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy, regardless of PD-L1 status.


  1. FDA Approves Updated Indication for Merck’s KEYTRUDA® (pembrolizumab) for Treatment of Certain Patients With Urothelial Carcinoma (Bladder Cancer). News release. Merck. August 31, 2021. Accessed August 31, 2021. https://bit.ly/3zxOktL
  2. Powles T, Csőszi T, Özgüroğlu M, et al. Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(7):931-945. doi:10.1016/S1470-2045(21)00152-2
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