Trastuzumab deruxtecan (T-DXd) vs ramucirumab (RAM) + paclitaxel (PTX) in second-line treatment of patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) unresectable/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary analysis of the randomized, phase 3 DESTINY-Gastric04 study.

作者：Kohei Shitara, Mahmut Gümüş, Filippo Pietrantonio, Sara Lonardi, Christelle De La Fouchardiere, Clélia Coutzac, Jeroen Dekervel, Daniel Hochhauser, Lin Shen, Wasat Mansoor, Bo Liu, Lorenzo Fornaro, Min‐Hee Ryu, Jeeyun Lee, Fabricio Souza, Lori Jukofsky, Yumin Zhao, Takahiro Kamio, Aziz Zaanan, Eric Van Cutsem · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.17_suppl.lba4002 · 被引用次数：10 · 研究领域：Gastric Cancer Management and Outcomes、Lung Cancer Treatments and Mutations、Colorectal Cancer Treatments and Studies

LBA4002 Background: T-DXd 6.4 mg/kg is approved for pts with metastatic HER2+ GC/GEJA who received a prior trastuzumab-based regimen based on prior phase 2 studies. This is the primary efficacy analysis from a planned interim analysis of DESTINY-Gastric04 (NCT04704934), a global, randomized, multicenter, open-label, phase 3 study evaluating the efficacy and safety of T-DXd vs RAM + PTX in pts with HER2+ unresectable/metastatic GC/GEJA in this second-line setting. Methods: After biopsy-confirmed HER2+ status (IHC 3+ or IHC 2+/ISH+), pts were randomized 1:1 to T-DXd 6.4 mg/kg or RAM + PTX. The primary endpoint was overall survival (OS). OS between the 2 arms was compared by a log-rank test stratified using randomization factors. Secondary endpoints by investigator assessment include progression-free survival (PFS), confirmed objective response rate (cORR), disease control rate (DCR), and safety. Results: At data cutoff (October 24, 2024), 494 pts were assigned (T-DXd, n = 246; RAM + PTX, n = 248). Based on 266 OS events observed (information fraction = 78.5%), efficacy superiority was achieved (2-sided P < 0.0228). Median (m) (95% CI) OS follow-up was 16.8 mo (14.0-20.0) for T-DXd and 14.4 mo (13.1-19.7) for RAM + PTX. mOS (95% CI) was 14.7 mo (12.1-16.6) for T-DXd vs 11.4 mo (9.9-15.5) for RAM + PTX (hazard ratio [HR], 0.70; P = 0.0044). Additional efficacy data are in the Table. Median (range) treatment duration was 5.4 mo (0.7-30.3) with T-DXd and 4.6 mo (0.9-34.9) with R...