The phase II single-arm KEYNOTE-052 study evaluated the efficacy and safety of first-line pembrolizumab for patients with locally advanced or metastatic cisplatin-ineligible urothelial carcinoma (UC).

Three hundred seventy patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months. Positive tumor programmed death ligand 1 (PD-L1) expression was defined as combined positive score (CPS) ≥ 10. Response was assessed by independent central review every 9 weeks per RECIST v1.1. The primary end point was objective response rate (ORR).

At data cutoff (September 26, 2018), the minimum follow-up was 2 years since the last patient enrolled. ORR was 28.6% (95% CI, 24.1% to 33.5%); 33 patients (8.9%) and 73 patients (19.7%) achieved complete and partial response, respectively. The median duration of response was 30.1 months (95% CI, 18.1 months to not reached [NR]); responses lasted ≥ 12 and ≥ 24 months in 67% and 52% of patients, respectively. Forty patients with complete or partial response completed 2 years of study treatment, and 32 had ongoing response at completion. Median overall survival (OS) was 11.3 months (95% CI, 9.7 to 13.1 months), and 12- and 24-month OS rates were 46.9% and 31.2%, respectively. In patients with CPS ≥ 10, ORR was 47.3% (95% CI, 37.7% to 57.0%) and median OS was 18.5 months (95% CI, 12.2 to 28.5 months). In patients with lymph node-only disease, ORR was 49.0% (95% CI, 34.8% to 63.4%), and median OS was 27.0 months (12.4 months to NR). There were no new safety signals.

First-line pembrolizumab confers meaningful and durable clinical response in cisplatin-ineligible patients with advanced UC and is associated with prolonged OS, particularly with PD-L1 CPS ≥ 10 and lymph node-only disease.