Pembrolizumab (MK-3475) for advanced urothelial cancer: Updated results and biomarker analysis from KEYNOTE-012.

Genitourinary (Nonprostate) Cancer
Session Type and Session Title: 
Oral Abstract Session, Genitourinary (Nonprostate) Cancer
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 4502)
Elizabeth R. Plimack, Joaquim Bellmunt, Shilpa Gupta, Raanan Berger, Robert B. Montgomery, Karl Heath, Jonathan Juco, Kenneth Emancipator, Kumudu Pathiraja, Jared K. Lunceford, Rodolfo F. Perini, Peter H. O'Donnell; Director, Genitourinary Clinical Research Fox Chase Cancer Center, Philadelphia, PA; Director, Bladder Cancer Center Dana-Farber Cancer Institute, Boston, MA; Department of Genitourinary Oncology H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Director, Division of Medical Oncology Sheba Medical Center, Tel Hashomer, Israel; University of Washington Oncology, Seattle, WA; Merck & Co., Inc., Kenilworth, NJ; The University of Chicago, Chicago, IL

Abstract Disclosures


Background: Pembrolizumab, an anti–PD-1 antibody, demonstrated antitumor activity and acceptable safety in patients with recurrent or metastatic PD-L1–positive urothelial cancer enrolled in the phase 1b KEYNOTE-012 study (NCT01848834). We present updated efficacy and safety data for these patients, as well as an analysis of the relationship between PD-L1 expression and ORR. Methods: Eligible patients had recurrent, metastatic, or persistent urothelial cancer of the bladder, renal pelvis, ureter, or urethra. Patients received pembrolizumab 10 mg/kg every 2 weeks until complete response, progression, or unacceptable toxicity. PD-L1 expression was evaluated in baseline tumor samples at a central laboratory. Patients were enrolled if there were ≥1% PD-L1–positive cells in tumor nests or a PD-L1–positive band in stroma by a prototype immunohistochemistry assay. Samples were also analyzed with the clinical trial immunohistochemistry assay. Response was evaluated every 8 weeks per RECIST v1.1 by central review. Results: Thirty-three patients were enrolled (median age, 70 years; ≥3 prior therapies, 33%; visceral or osseous metastases, 66%). Median follow-up duration was 13 months (range, 1-16). Grade 3-4 drug-related adverse events occurred in 5 (15%) patients. In the 28 patients with measurable disease at baseline, ORR was 25% (95% CI 11-45), with 3 (11%) complete and 4 (14%) partial responses per central review. At the time of analysis, median duration of response had not been reached (range, 16-50+ weeks). The 12-month PFS rate was 19%. ORR in patients with tumors positive for PD-L1 expression as assessed with the clinical trial assay was 38%. Conclusions: Pembrolizumab demonstrates durable antitumor activity in patients with advanced urothelial cancer. A higher response rate was seen in patients with PD-L1 expression. Further analysis of the relationship between response and predictive biomarkers is ongoing. Clinical trial information: NCT01848834