Y Cao1, S Qin2, S Luo3, Z Li4, Y Cheng5, Y Fan6, Y Sun7, X Yin8, X Yuan9, W Li10, T Liu11, C-H Hsu12, X Lin13, S-B Kim14, T Kojima15, J Zhang16, S-H Lee17, Y Bai18, K Muro19, T Doi15, C Bai20, K Gu21, H-M Pan22, L Bai23, J-W Yang24, Y Cui25, W Lu25, J Chen26. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China. Electronic address: yanshuo.cao@icloud.com. 2. PLA Cancer Centre of Nanjing Bayi Hospital, Nanjing, China. 3. The Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China. 4. Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. 5. Jilin Cancer Hospital, Jilin, China. 6. Cancer Hospital of University of Chinese Academy of Sciences, Institute of Cancer and Basic Medicine of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China. 7. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, and The Affiliated Hospital of Anhui Medical University, Hefei, China. 8. Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. 9. Tongji Hospital, Wuhan, China. 10. Hubei Cancer Hospital, Wuhan, China. 11. Zhongshan Hospital, Fudan University, Shanghai, China. 12. National Taiwan University Hospital, Taipei, Taiwan. 13. Fujian Medical University Union Hospital, Fuzhou, China. 14. Asan Medical Center, Seoul, South Korea. 15. National Cancer Center Hospital East, Kashiwa, Japan. 16. Ruijin Hospital, Shanghai, China. 17. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 18. Harbin Medical University Cancer Hospital, Harbin, China. 19. Aichi Cancer Center Hospital, Nagoya, Japan. 20. Peking Union Medical College Hospital, Beijing, China. 21. The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China. 22. Sir Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China. 23. Chinese PLA General Hospital, Beijing, China. 24. Fujian Province Cancer Hospital, Fuzhou, China. 25. MSD China, Shanghai, China. 26. Jiangsu Cancer Hospital, Nanjing, China.
Abstract
BACKGROUND: In the randomized phase III KEYNOTE-181 study, pembrolizumab prolonged overall survival (OS) compared with chemotherapy as second-line therapy in patients with advanced esophageal cancer and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥10. We report a post hoc subgroup analysis of patients with esophageal squamous cell carcinoma (ESCC) enrolled in KEYNOTE-181 in Asia, including patients from the KEYNOTE-181 China extension study. PATIENTS AND METHODS: Three hundred and forty Asian patients with advanced/metastatic ESCC were enrolled in KEYNOTE-181, including the China cohort. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200 mg every 3 weeks for ≤2 years or investigator's choice of paclitaxel, docetaxel, or irinotecan. OS, progression-free survival, response, and safety were analyzed without formal comparisons. OS was evaluated based on PD-L1 CPS expression level. RESULTS: In Asian patients with ESCC, median OS was 10.0 months with pembrolizumab and 6.5 months with chemotherapy [hazard ratio (HR), 0.63; 95% CI 0.50-0.80; nominal P < 0.0001]. Median progression-free survival was 2.3 months with pembrolizumab and 3.1 months with chemotherapy (HR, 0.79; 95% CI 0.63-0.99; nominal P = 0.020). Objective response rate was 17.1% with pembrolizumab and 7.1% with chemotherapy; median duration of response was 10.5 months and 7.7 months, respectively. In patients with PD-L1 CPS <1 tumors (pembrolizumab versus chemotherapy), the HR was 0.99 (95% CI 0.56-1.72); the HR (95% CI) for death was better for patients with PD-L1 CPS cut-offs >1 [CPS ≥1, 0.57 (0.44-0.75); CPS ≥5, 0.56 (0.41-0.76); CPS ≥10, 0.53 (0.37-0.75)]. Treatment-related adverse events were reported in 71.8% of patients in the pembrolizumab group and 89.8% in the chemotherapy group; grade 3-5 events were reported in 20.0% and 44.6%, respectively. CONCLUSIONS: Pembrolizumab monotherapy demonstrated promising efficacy in Asian patients with ESCC, with fewer treatment-related adverse events than chemotherapy. PD-L1 CPS ≥1 is an appropriate cut-off and a predictive marker of pembrolizumab efficacy in Asian patients with ESCC.
BACKGROUND: In the randomized phase III KEYNOTE-181 study, pembrolizumab prolonged overall survival (OS) compared with chemotherapy as second-line therapy in patients with advanced esophageal cancer and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥10. We report a post hoc subgroup analysis of patients with esophageal squamous cell carcinoma (ESCC) enrolled in KEYNOTE-181 in Asia, including patients from the KEYNOTE-181 China extension study. PATIENTS AND METHODS: Three hundred and forty Asian patients with advanced/metastatic ESCC were enrolled in KEYNOTE-181, including the China cohort. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200 mg every 3 weeks for ≤2 years or investigator's choice of paclitaxel, docetaxel, or irinotecan. OS, progression-free survival, response, and safety were analyzed without formal comparisons. OS was evaluated based on PD-L1 CPS expression level. RESULTS: In Asian patients with ESCC, median OS was 10.0 months with pembrolizumab and 6.5 months with chemotherapy [hazard ratio (HR), 0.63; 95% CI 0.50-0.80; nominal P < 0.0001]. Median progression-free survival was 2.3 months with pembrolizumab and 3.1 months with chemotherapy (HR, 0.79; 95% CI 0.63-0.99; nominal P = 0.020). Objective response rate was 17.1% with pembrolizumab and 7.1% with chemotherapy; median duration of response was 10.5 months and 7.7 months, respectively. In patients with PD-L1 CPS <1 tumors (pembrolizumab versus chemotherapy), the HR was 0.99 (95% CI 0.56-1.72); the HR (95% CI) for death was better for patients with PD-L1 CPS cut-offs >1 [CPS ≥1, 0.57 (0.44-0.75); CPS ≥5, 0.56 (0.41-0.76); CPS ≥10, 0.53 (0.37-0.75)]. Treatment-related adverse events were reported in 71.8% of patients in the pembrolizumab group and 89.8% in the chemotherapy group; grade 3-5 events were reported in 20.0% and 44.6%, respectively. CONCLUSIONS: Pembrolizumab monotherapy demonstrated promising efficacy in Asian patients with ESCC, with fewer treatment-related adverse events than chemotherapy. PD-L1 CPS ≥1 is an appropriate cut-off and a predictive marker of pembrolizumab efficacy in Asian patients with ESCC.