Long-Term Outcomes in KEYNOTE-052: Phase II Study Investigating First-Line Pembrolizumab in Cisplatin-Ineligible Patients With Locally Advanced or Metastatic Urothelial Cancer

• Published in: Journal of clinical oncology Vol. 38; no. 23; pp. 2658 - 2666
• Main Authors: Vuky, Jacqueline, Balar, Arjun V, Castellano, Daniel, O'Donnell, Peter H, Grivas, Petros, Bellmunt, Joaquim, Powles, Thomas, Bajorin, Dean, Hahn, Noah M, Savage, Mary J, Fang, Xiao, Godwin, James Luke, Frenkl, Tara L, Homet Moreno, Blanca, de Wit, Ronald, Plimack, Elizabeth R
• Format: Journal Article
• Language: English
• Published: United States 10-08-2020
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - adverse effects; B7-H1 Antigen - biosynthesis; B7-H1 Antigen - immunology; Cisplatin - administration & dosage; Humans; Middle Aged; Treatment Outcome; Urologic Neoplasms - drug therapy; Urologic Neoplasms - immunology
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.19.01213

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.