Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma

作者：Yuichiro Doki, Jaffer A. Ajani, Ken Kato, Jianming Xu, Lucjan Wyrwicz, Satoru Motoyama, Takashi Ogata, Hisato Kawakami, Chih-Hung Hsu, Antoine Adenis, Farid El Hajbi, Maria Di Bartolomeo, Maria I. Braghiroli, Eva Holtved, Sandra A. Ostoich, Hye R. Kim, Masaki Ueno, Wasat Mansoor, Wen-Chi Yang, Tianshu Liu, John Bridgewater, Tomoki Makino, Ioannis Xynos, Xuan Liu, Ming Lei, Kaoru Kondo, Apurva Patel, Joseph Gricar, Ian Chau, Yuko Kitagawa · 发表于：New England Journal of Medicine · 年份：2022 · DOI：10.1056/nejmoa2111380 · 被引用次数：1264 · 研究领域：Cancer Immunotherapy and Biomarkers、Esophageal Cancer Research and Treatment、CAR-T cell therapy research

BACKGROUND: First-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma. METHODS: In this open-label, phase 3 trial, we randomly assigned adults with previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamous-cell carcinoma in a 1:1:1 ratio to receive nivolumab plus chemotherapy, nivolumab plus the monoclonal antibody ipilimumab, or chemotherapy. The primary end points were overall survival and progression-free survival, as determined by blinded independent central review. Hierarchical testing was performed first in patients with tumor-cell programmed death ligand 1 (PD-L1) expression of 1% or greater and then in the overall population (all randomly assigned patients). RESULTS: A total of 970 patients underwent randomization. At a 13-month minimum follow-up, overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both among patients with tumor-cell PD-L1 expression of 1% or greater (median, 15.4 vs. 9.1 months; hazard ratio, 0.54; 99.5% confidence interval [CI], 0.37 to 0.80; P<0.001) and in the overall population (median, 13.2 vs. 10.7 months; hazard ratio, 0.74; 99.1% CI, 0.58 to 0.96; P = 0.002). Overall survival was also significantly longer with nivolumab plus ipilimumab than with chemoth...