Pembrolizumab as first-line therapy in cisplatin-ineligible advanced urothelial cancer: Results from the total KEYNOTE-052 study population.

Genitourinary Cancer
Session Type and Session Title: 
Poster Session B: Prostate Cancer and Urothelial Carcinoma
Abstract Number: 


Poster Board Number: 
Poster Session B Board #D21
J Clin Oncol 35, 2017 (suppl 6S; abstract 284)
Arjun Vasant Balar, Daniel E. Castellano, Peter H. O'Donnell, Petros Grivas, Jacqueline Vuky, Thomas Powles, Elizabeth R. Plimack, Noah M. Hahn, Ronald De Wit, Lei Pang, Mary Savage, Rodolfo F. Perini, Stephen Michael Keefe, Dean F. Bajorin, Joaquim Bellmunt; 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; Oregon Health & Science University, Portland, OR; Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Fox Chase Cancer Center, Philadelphia, PA; Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Erasmus MC Cancer Institute, Rotterdam, Netherlands; Merck & Co., Inc., Kenilworth, NJ; Memorial Sloan Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA

Abstract Disclosures


Background: Treatment options are limited for patients (pts) with advanced urothelial cancer (UC) ineligible to receive cisplatin-based chemotherapy. Interim results from the first 100 pts enrolled in the phase 2, open-label KEYNOTE-052 (ClinicalTrials.gov, NCT02335424) study suggested first-line pembrolizumab (pembro) had antitumor activity and acceptable safety in this pt population. Results from the fully enrolled study are presented. Methods: Key eligibility criteria included age ≥ 18 y, advanced UC of the renal pelvis, ureter, bladder, or urethra, cisplatin ineligibility (ECOG PS 2, creatinine clearance ≥ 30 to < 60 mL/min, grade ≥ 2 neuropathy or hearing loss, NYHA Class 3 heart failure), no prior systemic chemotherapy for advanced UC, measurable disease per RECIST v1.1, ECOG PS 0-2, and provision of a tumor sample for biomarker analyses. Pembro 200 mg was administered every 3 wk. Imaging was performed at wk 9, then every 6 wk for the first year, and every 12 wk thereafter. The primary end point was confirmed overall response rate (ORR; RECIST v1.1, independent review). Efficacy data are presented for pts with ≥ 4 mo follow-up, and safety data are presented for all pts. Results: In total, 370 pts were enrolled; median age was 74 y (range, 34-94 y); 42% had an ECOG PS 2. Reasons for cisplatin ineligibility included ECOG PS 2 (32%), renal dysfunction (49%), and both ECOG PS 2 and renal dysfunction (10%). ORR (95% CI) was 27% (22%-32%) among pts with ≥ 4 mo follow-up (n = 307); 6% of pts achieved a complete response. Among the ≥ 4 mo follow-up group, median (range) time to response was 2.0 (1.6-4.8) mo; median (range) duration of response was not reached (1+ to 14+ mo). 78% of responders had a response for ≥ 6 mo (KM estimate). PFS and OS rates at 6 mo were 31% and 67%, respectively (KM estimate). Any grade and grade ≥ 3 drug-related AEs occurred in 229 (62%) and 58 (16%) pts. 19 (5%) pts discontinued treatment because of a drug-related AE. Conclusions: Results from the fully enrolled KEYNOTE-052 study confirm that pembro elicits clinically meaningful and durable responses in cisplatin-ineligible pts with UC, including elderly pts and those with poor performance status. Clinical trial information: NCT02335424