Updated efficacy and safety of KEYNOTE-052: A single-arm phase 2 study investigating first-line pembrolizumab (pembro) in cisplatin-ineligible advanced urothelial cancer (UC).


Based on initial results from the phase 2 KEYNOTE-052 study (NCT02335424), pembro was approved for the treatment of cisplatin-ineligible patients with advanced UC. The results of the long-term follow-up analysis of KEYNOTE-052 are presented.


Eligible patients were cisplatin ineligible (ECOG PS 2, CrCl ≥30 to <60 mL/min, grade ≥2 neuropathy/hearing loss, NYHA Class 3 heart failure), had advanced UC, and had received no prior chemotherapy for metastatic disease. Patients received pembro 200 mg IV Q3W for up to 24 months. Imaging was performed at wk 9, then Q6W for 12 months, and Q12W thereafter. The primary end point was confirmed ORR (RECIST v1.1, independent central review). 


Efficacy and safety were assessed in 370 patients. Median age was 74 years; 10.8% of patients were ≥85 years old; 42.2% were ECOG PS 2; and 85.1% had visceral disease. As of the Nov 30, 2017, data cutoff, median (range) follow-up was 11.5 (0.1-31.3) mo. Confirmed ORR was 28.9% (95% CI, 24.3-33.8); 30 (8.1%) and 77 (20.8%) patients had complete response and partial response, respectively. Median duration of response was not reached (NR) (95% CI, 21.4 mo to NR); 82% and 68% of patients had a response of ≥6 and ≥12 mo, respectively. Median OS was 11.5 (95% CI, 10.0-13.3) mo; 6-and 12-mo OS rates were 67.2% and 47.5%, respectively. In patients with a PD-L1 expression combined positive score of ≥10 (n=110), ORR was 47.3% (95% CI, 37.7-57.0) and median OS was 18.5 mo (95% CI, 12.2 mo to NR). Median OS was NR (12.4 mo to NR) in patients with lymph node–only disease (n=51) and was 13.1 (95% CI, 11.0-16.8) mo in patients with ECOG PS 0/1 (n=214) and 9.7 (95% CI, 5.7-11.6) mo in patients with ECOG PS 2 (n=156). Treatment-related adverse events (AEs) occurred in 67.6% of patients; most common (≥15%) were fatigue (18.1%) and pruritus (17.8%). Grade ≥3 treatment-related AEs occurred in 20.3% of patients. Immune-mediated AEs occurred in 24.6% of patients. 


Pembro continues to be well tolerated and elicits clinically meaningful, durable antitumor activity in a broad spectrum of cisplatin-ineligible patients with advanced UC. Clinical trial information: NCT02335424.

Jacqueline Vuky, Arjun Vasant Balar, Daniel E. Castellano, Peter H. O'Donnell, Petros Grivas, Joaquim Bellmunt, Thomas Powles, Dean F. Bajorin, Noah M. Hahn, Ronald De Wit, Mary Savage, Lei Pang, Tara L. Frenkl, Stephen Michael Keefe, Elizabeth R. Plimack 

Oregon Health & Science University, Portland, OR; Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY; Hospital Universitario 12 de Octubre, Madrid, Spain; The University of Chicago Medical Center, Chicago, IL; Cleveland Clinic, Cleveland, OH; Dana-Farber Cancer Institute, Boston, MA; Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Memorial Sloan Kettering Cancer Center, New York, NY; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Erasmus MC Cancer Institute, Rotterdam, Netherlands; Merck & Co., Inc., Kenilworth, NJ; Fox Chase Cancer Center, Philadelphia, PA