The Food and Drug Administration (FDA) has granted full approval and revised the indication for Keytruda® (pembrolizumab) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for any platinum-containing chemotherapy.
Previously, Keytruda was indicated for the treatment of patients with locally advanced or mUC who were not eligible for cisplatin-containing chemotherapy and whose tumors expressed PD-L1 (Combined Positive Score [CPS] ≥10), as determined by an FDA-approved test, or in patients who were not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication was granted accelerated approval based on tumor response rate and duration of response.
The full approval was based on data from the confirmatory phase 3 KEYNOTE-361 trial (ClinicalTrials.gov Identifier: NCT02853305), which assessed the efficacy and safety of pembrolizumab as monotherapy and in combination with chemotherapy for the first-line treatment of 1010 patients with locally advanced or mUC. Patients were randomly assigned 1:1:1 to receive pembrolizumab plus chemotherapy (investigator’s choice of cisplatin or carboplatin with gemcitabine), pembrolizumab alone, or chemotherapy alone.
Results showed that the trial did not meet the prespecified dual primary endpoints of overall survival or progression-free survival. The combination of pembrolizumab and chemotherapy did demonstrate the following numerical improvements in both primary endpoints after a median follow-up of 31.7 months compared with chemotherapy alone, respectively:
- Median progression-free survival: 8.3 months vs 7.1 months (hazard ratio, 0.78; 95% CI, 0.65-0.93; P =.0033).
- Median overall survival: 17.0 months vs 14.3 months (hazard ratio, 0.86; 95% CI, 0.72-1.02; P =.0407).
In April 2021, the FDA’s Oncologic Drugs Advisory Committee voted (5-3) in favor of maintaining the accelerated approval of Keytruda for the first-line treatment of urothelial carcinoma.
“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 Dr Scot Ebbinghaus, 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.”
Keytruda, a programmed death receptor-1-blocking antibody, is also approved for the treatment of patients with locally advanced or mUC who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
- FDA approves updated indication for Merck’s Keytruda® (pembrolizumab) for treatment of certain patients with urothelial carcinoma (bladder cancer). News release. Merck & Co., Inc. August 31, 2021. Accessed September 1, 2021. https://www.businesswire.com/news/home/20210831005968/en/FDA-Approves-Updated-Indication-for-Merck%E2%80%99s-KEYTRUDA%C2%AE-pembrolizumab-for-Treatment-of-Certain-Patients-With-Urothelial-Carcinoma-Bladder-Cancer.
- 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 randomized, open-label, phase 3 trial. Lancet Oncol. 2021;22(7):931-945. doi:10.1016/S1470-2045(21)00152-2
- Merck Provides Update on FDA’s Oncologic Drugs Advisory Committee (ODAC) Meetings on April 28-29, 2021. News release. Merck & Co., Inc. Accessed September 1, 2021. https://www.merck.com/news/fdas-oncologic-drugs-advisory-committee-to-discuss-three-indications-for-keytruda-pembrolizumab-during-meetings-focused-on-accelerated-approvals-2/.