ASCO 2017: Phase 3 KEYNOTE-361 trial: Pembrolizumab with or without chemotherapy versus chemotherapy alone in advanced urothelial cancer

Chicago, IL ( At the genitourinary cancer poster session at the 2017 ASCO annual meeting, Dr. Powles and colleagues presented the design of their phase III KEYNOTE-361 trial randomizing pembrolizumab with or without chemotherapy alone in patients with advanced urothelial carcinoma. Since only 5%-15% of patients with advanced bladder cancer attain long-term survival with standard first-line cisplatin-based chemotherapy, additional therapies are desperately needed. Certainly, we have seen immunotherapy oncologic efficacy in the metastatic bladder setting [1], with atezolizumab receiving breakthrough designation status by the FDA in June 2014. In KEYNOTE-052, first-line pembrolizumab, an anti–PD-1 antibody, demonstrated antitumor activity and acceptable safety in cisplatin-ineligible patients with advanced urothelial cancer [2].

For the phase III KEYNOTE-361 trial, key eligibility criteria include: (i) age ≥18 years, (ii) histologically or cytologically confirmed unresectable/metastatic urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, (iii) measurable disease (RECIST v1.1), (iv) no prior systemic chemotherapy, (v) ECOG performance status 0-2, and (vi) provision of a tumor sample for biomarker analyses. Patients treated with [neo]adjuvant platinum-based chemotherapy with recurrence > 12 months after completion will be allowed to enroll. Patients will be randomized 1:1:1 to receive pembrolizumab 200 mg every 3 weeks, pembrolizumab + investigator’s choice of chemotherapy (gemcitabine [1000 mg/m2 on day 1 and 8 every three weeks] + cisplatin [70 mg/m2 every three weeks]), or chemotherapy alone. Patients that are cisplatin-ineligible randomized to chemotherapy will receive gemcitabine + carboplatin [AUC 5 every 3 weeks]. Treatment will continue until progressive disease, unacceptable adverse events, or 35 cycles of pembrolizumab in the pembrolizumab arms only. Responses will be assessed every 9 weeks for the first year and then every 12 weeks thereafter. Primary end points are progression-free survival (RECIST v1.1) and overall survival, while secondary end points include objective response rate, safety, and tolerability. Efficacy outcomes will be compared for pembrolizumab vs chemotherapy and pembrolizumab + chemotherapy vs chemotherapy.

This trial is currently ongoing, current enrolling patients in 22 countries with a target enrollment of 990 patients. We eagerly await the results of this important phase III study in patients with metastatic urothelial carcinoma.
Clinical trial: NCT02853305

Presented By: Thomas Powles, Barts Cancer Institute, London, UK

Co-Authors: Juergen E. Gschwend, Yohann Loriot, Joaquim Bellmunt, Lajos Geczi, Christof Vulsteke, Mahmoud Abdelsalam, Rustem Gafanov, Woo Kyun Bae, Janos Revesz, Yoshiaki Yamamoto, Urbano Anido, Wen-Pin Su, Mark T. Fleming, Maurice Markus, Dai Feng, Christian Heinrich Poehlein, Ajjai Alva

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA


1. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014 Nov 27;515(7528):558-562.
2. Balar A, Bellmunt J, O’Donnell PH, et al. Pembrolizumab (pembro) as first-line therapy for advanced/unresectable or metastatic urothelial cancer: Preliminary results from the phase 2 KEYNOTE-052 study. Ann Oncol 2016;27(suppl_6):LBA32_PR.