Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer

作者：Kohei Shitara, Eric Van Cutsem, Mahmut Gümüş, Sara Lonardi, Christelle de la Fouchardière, Clélia Coutzac, Jeroen Dekervel, Daniel Hochhauser, Lin Shen, Wasat Mansoor, Bo Liu, Lorenzo Fornaro, Min-Hee Ryu, Jeeyun Lee, C. Faustino, Jean‐Philippe Metges, Josep Tabernero, Fábio Franke, Yelena Y. Janjigian, Fabricio Souza, Lori Jukofsky, Yumin Zhao, Takahiro Kamio, Aziz Zaanan, Filippo Pietrantonio · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2503119 · 被引用次数：101 · 研究领域：Gastric Cancer Management and Outcomes、HER2/EGFR in Cancer Research、Peptidase Inhibition and Analysis

BACKGROUND: On the basis of phase 2 studies, trastuzumab deruxtecan was approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma who had previously received trastuzumab-based therapy. Ramucirumab plus paclitaxel is also a standard second-line treatment option regardless of HER2 status. METHODS: We conducted an international, randomized, phase 3 trial comparing second-line trastuzumab deruxtecan at a dose of 6.4 mg per kilogram of body weight with ramucirumab plus paclitaxel in patients with HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma confirmed on tumor biopsy conducted after the patient had progression while receiving trastuzumab-based therapy. The primary end point was overall survival. Secondary end points included progression-free survival, confirmed objective response (complete or partial response lasting ≥4 weeks), disease control, duration of response, and safety. RESULTS: Among 494 patients who had undergone randomization, overall survival was significantly longer with trastuzumab deruxtecan than with ramucirumab plus paclitaxel (median, 14.7 vs. 11.4 months; hazard ratio for death, 0.70; 95% confidence interval, 0.55 to 0.90; P = 0.004). Significant results were also seen with regard to progression-free survival (hazard ratio for disease progression or death, 0.74; 95% CI, 0.59 to 0.92) and confirmed objective response (in 44.3% of t...