Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer

作者：Kohei Shitara, Elena Elimova, T Liu, Josep Tabernero, Keun-Wook Lee, Michael Schenker, N. C. Tebbutt, J AJANI, N. Salimin, Geoffrey Ku, Jong Gwang Kim, Inmaculada Alés Díaz, Jingdong Zhang, Filippo Pietrantonio, Li-Yuan Bai, Samuel Le Sourd, Jun Zhao, Cinta Hierro, Andrew Kiberu, Filip Van Herpe, Yuanyuan Bao, Hanze Zhang, Lin Yang, Vincent Li, Elaina M. Gartner, Ye Chen, Jonathan Grim, Sun Young Rha, L Shen · 发表于：New England Journal of Medicine · 年份：2026 · DOI：10.1056/nejmoa2517729 · 被引用次数：8 · 研究领域：HER2/EGFR in Cancer Research、Cancer Immunotherapy and Biomarkers、Colorectal Cancer Treatments and Studies

BACKGROUND: Zanidatamab, a dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, plus chemotherapy both with and without tislelizumab (anti-programmed death 1), showed encouraging efficacy and safety as first-line therapy in phase 2 studies involving patients with HER2-positive gastroesophageal adenocarcinoma. METHODS: In an open-label, phase 3 trial, we randomly assigned, in a 1:1:1 ratio, patients with previously untreated, centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma to receive zanidatamab and tislelizumab plus chemotherapy, zanidatamab plus chemotherapy, or trastuzumab plus chemotherapy. The two primary end points were progression-free survival and overall survival. RESULTS: At a median follow-up of 25.9 months, progression-free survival was longer with zanidatamab-tislelizumab-chemotherapy (median among 302 patients, 12.4 months) and zanidatamab-chemotherapy (median among 304 patients, 12.4 months) than with trastuzumab-chemotherapy (median among 308 patients, 8.1 months) (hazard ratio for progression or death with zanidatamab-tislelizumab-chemotherapy, 0.63 [95% confidence interval {CI}, 0.51 to 0.78]; hazard ratio with zanidatamab-chemotherapy, 0.65 [95% CI, 0.52 to 0.81]; P<0.001 for both comparisons). Overall survival was longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy (median, 26.4 vs. 19.2 months; hazard ratio for death, 0.72; 95% CI, 0.57 to 0.90; P = 0.004). At this in...