The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan).
Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off). Dual primary endpoints were OS and PFS, assessed by blinded independent central review. Secondary endpoints were objective response rate (ORR) and safety.
The East Asian subgroup comprised 130 patients (pembrolizumab-axitinib, n = 62; sunitinib, n = 68; 15.1% of the global intention-to-treat population). Compared with sunitinib, pembrolizumab-axitinib OS hazard ratio (HR) was 0.85 [95% confidence interval (CI) 0.50-1.44; 36-month rates, 62.9% and 58.8%, respectively] and PFS HR was 0.59 (95% CI 0.38-0.92) in favor of pembrolizumab-axitinib. ORR favored pembrolizumab-axitinib (64.5% vs 44.1% for sunitinib). The results were generally consistent with the intention-to-treat population. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 69.4% of patients on pembrolizumab-axitinib and 74.6% on sunitinib; 16 (25.8%) patients on pembrolizumab-axitinib and 17 (25.4%) patients on sunitinib discontinued due to adverse events. No deaths from TRAEs occurred.
Pembrolizumab-axitinib improved efficacy for East Asian patients with untreated clear cell mRCC, consistent with results from the global population. Safety was manageable. ClinicalTrials.gov identifier: NCT02853331.
Japanese journal of clinical oncology. 2025 Jan 16 [Epub ahead of print]
Hsiao-Jen Chung, Chihiro Kondoh, Woo Kyun Bae, Satoshi Tamada, Nobuaki Matsubara, Hyo Jin Lee, Ryuichi Mizuno, Satoshi Anai, Go Kimura, Yoshihiko Tomita, Chao-Hsiang Chang, John Wen-Cheng Chang, Jianxin Lin, Rodolfo F Perini, L Rhoda Molife, Thomas Powles, Brian I Rini, Hirotsugu Uemura
Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 11217, Taiwan., Toranomon Hospital, 2 Chome-2-2 Toranomon, Minato City, Tokyo 105-8470, Japan., Chonnam National University Hospital and College of Medicine, Gwangju, Dong-gu, Baekseo-ro, 160, Hwasun, Republic of Korea., Osaka Metropolitan University, 599-8247 Higashiyama 500-3 Naka-ku, Sakai City, Osaka, Japan., National Cancer Center Hospital East, $\overline\top$277-8577 Chiba, Kashiwa, Kashiwanoha, 6 Chome-5-1, Japan., Chungnam National University School of Medicine, 266 Munhwa-ro, Jung-gu, Daejeon, Republic of Korea., Keio University Hospital, 35 Shinanomachi, Shinjuku City, Tokyo 160-0016, Japan., Nara Medical University Hospital, 1 Chome-14-16 Mimuro, Sango, Ikoma District, Nara 636-0802, Kashihara, Japan., Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan., Niigata University Medical & Dental Hospital, 1 Bancho-754 Asahimachidori, Chuo Ward, Niigata, 951-8122, Japan., China Medical University Hospital, No. 2, Yude Road, North District, Taichung City 404327, Taiwan., Chang Gung University College of Medicine, No. 259, Wenhua 1st Rd, Guishan District, Taoyuan City, Taiwan 333, Taiwan., Merck & Co., Inc, 2025 E Scott Ave, 07065, Rahway, NJ, United States., MSD UK, 2 St Pancras Square, N1C 1AG, London, United Kingdom., Barts Health NHS Trust and the Royal Free NHS Foundation Trust, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, EC1M 6AU, London, United Kingdom., Cleveland Clinic Taussig Cancer Institute, 2220 Pierce Ave, 44195, Cleveland, OH, United States., Kindai University Hospital, 377-2 Onohigashi, Osakasayama, 589-8511, Osaka, Japan.