The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan.
Analysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points.
Fifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44-1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32-1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95-3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3-5 events, occurred less frequently with pembrolizumab.
Pembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab.
International journal of clinical oncology. 2019 Nov 15 [Epub ahead of print]
Hiroyuki Nishiyama, Yoshiaki Yamamoto, Naoto Sassa, Kazuo Nishimura, Kiyohide Fujimoto, Satoshi Fukasawa, Minato Yokoyama, Hideki Enokida, Kenichi Takahashi, Yoshinobu Tanaka, Kentaro Imai, Takashi Shimamoto, Rodolfo Perini, Tara Frenkl, Dean Bajorin, Joaquim Bellmunt
University of Tsukuba Hospital, 2 Chome-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan. ., Yamaguchi University Hospital, 1 Chome-1-1 Minamikogush, Ube, Japan., Nagoya University Hospital, 65 Tsurumaicho, Showa Ward, Nagoya, Japan., Osaka International Cancer Institute, 3 Chome-1-6 9 Otemae, Chuo Ward, Osaka, Japan., Nara Medical University Hospital, 840 Shijocho, Kashihara, Japan., Chiba Cancer Center, 666-2 Nitonacho, Chiba, Japan., Medical Hospital, Tokyo Medical and Dental University, 1 Chome-5-45 Yushima, Tokyo, Japan., Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, Japan., MSD K.K., Kitanomaru Square, 1-13-12, Kudan Kita, Tokyo, Japan., Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ, USA., Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA., PSMAR-IMIM Research Institute, Carrer del Dr. Aiguader, 88, Barcelona, Spain.