Pembrolizumab Granted Full FDA Approval for Urothelial Carcinoma

The FDA has approved pembrolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for any platinum-containing chemotherapy. 

The FDA has approved pembrolizumab (Keytruda) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for any platinum-containing chemotherapy, according to a press release by Merck.

Previously, pembrolizumab was granted an accelerated approval by the FDA. The FDA Oncologic Drugs Advisory Committee (ODAC) voted 5-3 in favor of continuing the approval of pembrolizumab for mUC after it failed to meet post-marketing requirements.

“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,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories. “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.”

Approval is based on the results of the phase 3 KEYNOTE-361 trial (NCT02853305), which enrolled 1010 participants. The study had a primary end point of progression-free survival (PFS) and overall survival (OS). Secondary end points include the rate of adverse events (AEs), rate of discontinuation, objective response rate, duration of response, and disease control rate.

During the study patients were randomized to receive either pembrolizumab alone, chemotherapy alone, or a combination of chemotherapy and pembrolizumab.

Primary end points were not reached. In the combination group, 54.7% had a response compared to 30.3% in the pembrolizumab group, and 44.9% in the chemotherapy group. Complete response rate for the combination group was 15%, 11% for pembrolizumab group, and 12% for the chemotherapy group. Partial responses stood at 40% for the combination group, 19% for the pembrolizumab group, and 33% for the chemotherapy group. Stable disease was seen in 26% of patients in the combination group, 17% of patients in the pembrolizumab group, and 31% of patients in the chemotherapy group. Progressive disease was seen in 11% of patients in both the combination and chemotherapy groups, and 38% of patients in the pembrolizumab group.

Grade 1-2 AEs were seen in 99% of the combination group, 94% of the pembrolizumab group, and 99% of the chemotherapy group. Grade 5 AEs were seen in 9% of the combination and pembrolizumab groups, and 3% of the chemotherapy group. Anemia was the most common any-grade AE. The most common AEs attributed to pembrolizumab monotherapy was anemia and fatigue.

In order to participate in the study, patients must have confirmed mUC, have measurable disease, have received no prior systemic chemotherapy for mUC, demonstrate adequate organ function, and an ECOG score between 0-2. Patients with disease that is suitable for local therapy, an active autoimmune disease, an active infection, or a known history of HIV are not eligible to participate.


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.

2. Study of pembrolizumab with or without platinum-based combination chemotherapy versus chemotherapy alone in urothelial carcinoma (MK-3475-361/KEYNOTE-361). Accessed August 31, 2021.

3. Powels T, Csosi T, Özgüroglu 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: