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

Chicago, IL (UroToday.com) 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

References:

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.
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