Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer

作者：Yelena Y. Janjigian, Salah-Eddin Al-Batran, Zev A. Wainberg, Kei Muro, Daniela Molena, Eric Van Cutsem, Woo Jin Hyung, Lucjan Wyrwicz, Do-Youn Oh, Takeshi Omori, Markus Moehler, Marcelo Garrido, Sulene Cunha Sousa Oliveira, Moïshe Liberman, Victor Castro Oliden, Elizabeth Smyth, Alexander Stein, Mehmet Bilici, Maria Lorena Alvarenga, Vadim Kozlov, Fernando Rivera, Akihito Kawazoe, Olivier Serrano, Eric Heilbron, Alejandra Negro, John F. Kurland, Josep Tabernero · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2503701 · 被引用次数：287 · 研究领域：Gastric Cancer Management and Outcomes、Esophageal Cancer Research and Treatment、Colorectal and Anal Carcinomas

BACKGROUND: Perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) is a standard therapy for resectable gastric and gastroesophageal junction adenocarcinomas, but recurrence rates remain high. Immunotherapy plus chemotherapy may improve outcomes. METHODS: In a phase 3, multinational, double-blind, randomized trial, we assigned participants with resectable gastric or gastroesophageal junction adenocarcinoma, in a 1:1 ratio, to receive durvalumab at a dose of 1500 mg or placebo every 4 weeks plus FLOT for 4 cycles (2 cycles each of neoadjuvant and adjuvant therapy), followed by durvalumab or placebo every 4 weeks for 10 cycles. The primary end point was event-free survival; secondary end points included overall survival and pathological complete response. RESULTS: A total of 474 participants were randomly assigned to the durvalumab group, and 474 to the placebo group (median follow-up, 31.5 months; interquartile range, 26.7 to 36.6). Two-year event-free survival (Kaplan-Meier estimate) was 67.4% among the participants in the durvalumab group and 58.5% among those in the placebo group (hazard ratio for event or death, 0.71; 95% confidence interval [CI], 0.58 to 0.86; P<0.001). Two-year overall survival was 75.7% in the durvalumab group and 70.4% in the placebo group (piecewise hazard ratio for death during months 0 to 12, 0.99 [95% CI, 0.70 to 1.39], and during the period from month 12 onward, 0.67 [95% CI, 0.50 to 0.90]; P = 0.03 by a stratified log-rank test...