FDA Approves Pembrolizumab for Advanced/Metastatic Urothelial Carcinoma

Urothelial carcinoma.

The FDA has granted regular approval to pembrolizumab (Keytruda®, Merck) for the first-line treatment of patients with locally advanced/metastatic urothelial carcinoma who are ineligible for platinum-containing chemotherapy. This regular approval comes after the FDA granted pembrolizumab accelerated approval.

“Programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are active in metastatic urothelial carcinoma,” wrote Thomas Powles, MD, Professor of Genitourinary Oncology and Director of the Barts Cancer Centre in the United Kingdom, and colleagues, in their publication of the results of the KEYNOTE-361 trial in The Lancet Oncology, on which the regular approval was based (NCT02853305). “In this study, we assessed outcomes with first-line pembrolizumab versus chemotherapy for patients with previously untreated advanced urothelial carcinoma.”

In this open-label phase 3 trial, 1,010 patients enrolled and were randomized 1:1:1 to receive either 200 mg pembrolizumab intravenously every three weeks for a maximum of 35 cycles, plus 1,000 mg/m2 gemcitabine on Days 1 and 8 and investigator’s choice of 70 mg/m2 cisplatin or carboplatin on Day 1 of every three-week cycle for a maximum of 6 cycles; pembrolizumab alone; or chemotherapy alone. The primary end points were progression-free survival and overall survival.

At a median follow up of 31.7 months, pembrolizumab plus chemotherapy did not significantly improve progression-free survival, with patients in that treatment arm achieving a median progression-free survival of 8.3 months compared with 7.1 months in the chemotherapy treatment arm. Pembrolizumab plus chemotherapy also did not significantly improve overall survival, with patients in that treatment arm achieving a median overall survival of 17.0 months compared with 14.3 months in the chemotherapy treatment arm.

The most common adverse events occurring in at least 20% of patients receiving pembrolizumab with chemotherapy were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, and insomnia.

Although Dr. Powles and colleagues, in their July 2021 publication, discourage the wide adoption of pembrolizumab for the treatment of advanced urothelial carcinoma, the FDA’s Oncologic Drugs Advisory Committee voted 5-3 to continue approval of the drug being used for this specific indication.

The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks.

For More Information

Powles T, Csőszi T, Özgüroğlu M, et al (2021). 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, 22(7):931-945. DOI:10.1016/S1470-2045(21)00152-2

Merck (2021). FDA approves updated indication for Merck’s KEYTRUDA® (pembrolizumab) for treatment of certain patients with urothelial carcinoma (bladder cancer). Available at: https://www.merck.com/news/fda-approves-updated-indication-for-mercks-keytruda-pembrolizumab-for-treatment-of-certain-patients-with-urothelial-carcinoma-bladder-cancer/

Clinicaltrials.gov (2021). Study of pembrolizumab with or without platinum-based combination chemotherapy versus chemotherapy alone in urothelial carcinoma (MK-3475-361/KEYNOTE-361). NLM identifier: NCT02853305.

Keytruda® (pembrolizumab) prescribing information (2021). Merck. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s117,s118lbl.pdf

Image credit: CoRus13. Licensed under CC0 1.0

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