ESMO 2017: Pembrolizumab ± chemotherapy versus chemotherapy in advanced urothelial cancer: Phase 3 KEYNOTE-361 trial

Madrid, Spain ( Dr. Thomas Powles and his international colleagues presented their trial design for KEYNOTE-361, a phase III trial assessing pembrolizumab +/- chemotherapy vs chemotherapy for patients with advanced urothelial cancer.

Earlier this year, results were reported demonstrating a 3-month overall survival (OS) advantage for pembrolizumab (anti–PD-1) vs chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma [1]. Furthermore, data from KEYNOTE-052 presented at ESMO 2016 showed that first-line pembrolizumab had antitumor activity with an acceptable safety profile in cisplatin ineligible patients with advanced urothelial cancer [2]. This suggests that pembrolizumab may be effective as first-line treatment, a setting in which only 50% of patients can receive the current standard-of-care, cisplatin-based chemotherapy. The objective of this phase III randomized, open-label study is to assess first-line pembrolizumab ± chemotherapy versus chemotherapy in patients with advanced urothelial carcinoma.

Trial design: This study will accrue approximately 990 patients with histologically or cytologically confirmed unresectable/metastatic urothelial carcinoma. Patients will be randomly assigned 1:1:1 to pembrolizumab 200 mg every 3 weeks (Q3W), pembrolizumab + chemotherapy (investigator’s choice of cisplatin [70 mg/m Q3W] plus gemcitabine [1000 mg/m on days 1 and 8 Q3W] OR carboplatin [AUC 5 Q3W] plus gemcitabine if cisplatin ineligible), or chemotherapy alone. Key inclusion criteria include (i) patients having measurable disease per investigator review (RECIST v1.1), (ii) an ECOG performance status 0–2, (iii) received no prior systemic chemotherapy for advanced urothelial cancer, and (iv) provided a tumor biopsy. Treatment allocation will be stratified by chemotherapy (cisplatin or carboplatin) and PD-L1 expression (+ or –). Patients will be treated for 35 cycles of pembrolizumab (pembrolizumab arms only), or until progressive disease or unacceptable adverse events. The primary end points are progression-free survival (RECIST v1.1 per blinded independent central review) and OS, assessed in all patients and PD-L1+ patients. Secondary end points are objective response rate and safety. Efficacy will be compared for pembrolizumab versus chemotherapy and pembrolizumab + chemotherapy versus chemotherapy. This trial is currently accruing with an interim efficacy analysis planned. Clinical trial identification: NCT02853305


1. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376(11):1015-1026.

2. Balar A, Bellmunt J, O’Donnell PH, et al. LBA32_PR Pembrolizumab (pembro) as first-line therapy for advanced/unresectable or metastatic urothelial cancer: Preliminary results from the phase 2 KEYNOTE-052 study. 

Speaker: Thomas Powles, Barts Cancer Center, Queen Mary University of London, London, United Kingdom

Co-Authors: J. E. Gschwend (Munich, Germany) Y. Loriot (Villejuif, France) J. Bellmunt (Boston, United States of America) L. Geczi (Budapest, Hungary) C. Vulsteke (Antwerp, Belgium) M. Abdelsalam (Moncton, Canada) R. Gafanov (Moscow, Russian Federation) W. Bae (Hwasun, Korea, Republic of) J. Revesz (Miskolc, Hungary) Y. Yamamoto (Ube, Japan) U. Anido (Santiago de Compostela, Spain) W. Su (Tainan, Taiwan) M. Fleming (Norfolk, United States of America) M. Markus (Colorado Springs, United States of America) D. Feng (Kenilworth, United States of America) C. Poehlein (Kenilworth, United States of America) A. Alva (Ann Arbor, United States of America)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain