147894-156

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

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

4502

Citation: 
J Clin Oncol 33, 2015 (suppl; abstr 4502)
Author(s): 
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

Abstract: 

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