Abstract
Pembrolizumab is well tolerated and active in PD-L1–positive advanced or metastatic urothelial cancer.
Major finding: Pembrolizumab is well tolerated and active in PD-L1–positive advanced or metastatic urothelial cancer.
Approach: An open-label phase Ib trial evaluated the safety and activity of pembrolizumab.
Impact: Pembrolizumab may be safe and effective in patients with PD-L1–positive urothelial cancer.
New treatments are needed for patients with advanced urothelial cancer who have progressed on platinum-based chemotherapy. The inhibitory programmed death 1 (PD-1) receptor and its ligand PD-L1 are expressed in urothelial cancer, and PD-1 blockade has demonstrated antitumor activity in a variety of cancers including urothelial cancer. As part of the KEYNOTE-012 basket trial, Plimack and colleagues tested the safety and efficacy of the humanized monoclonal anti–PD-1 antibody pembrolizumab in an open-label phase Ib trial of patients with PD-1–positive advanced or metastatic urothelial cancer. The primary endpoints were safety, tolerability, and overall response. Secondary endpoints included progression-free and overall survival, and duration of response. Treatment-related adverse events occurred in 20 of 33 enrolled patients (61%), including serious treatment-related adverse events in 3 patients. The most common treatment-related adverse events were fatigue in 18% of patients and peripheral edema in 12% of patients. Of the 27 assessable patients, 7 (26%) achieved an overall response, including 3 complete and 4 partial responses, and 4 experienced stable disease. The median progression-free survival was 2 months, median overall survival was 13 months, and median duration of response was 10 months. Taken together, the results of this phase Ib trial suggest that pembrolizumab is well tolerated and exhibits durable antitumor activity in patients with PD-L1–positive urothelial cancers and support further clinical investigation in patients with these tumors.
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