Tislelizumab + Chemotherapy in Gastric Cancer: Long-Term RATIONALE-305 Randomized Trial Follow-up

作者：Marcia Cruz‐Correa, Do‐Youn Oh, Ken Kato, Josep Tabernero, Yuxian Bai, Jianhua Shi, Keun‐Wook Lee, Hidekazu Hirano, David R. Spigel, Lucjan Wyrwicz, Roberto Pazo-Cid, Antonio Cubillo Gracián, Yaling Xu, Tao Sheng, Silu Yang, Rui‐Hua Xu, Markus Moehler · 发表于：Advances in Therapy · 年份：2025 · DOI：10.1007/s12325-025-03415-0 · 被引用次数：2 · 研究领域：Gastric Cancer Management and Outcomes、Cancer Immunotherapy and Biomarkers、HER2/EGFR in Cancer Research

INTRODUCTION: Tislelizumab + chemotherapy has shown promising results as first-line treatment for advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC). We present long-term safety and efficacy outcomes from the RATIONALE-305 trial after 3 years of follow-up, focusing on the intent-to-treat (ITT) population and subgroups based on programmed death ligand-1 (PD-L1) expression. METHODS: RATIONALE-305, a randomized, double-blind, placebo-controlled, phase 3 trial conducted across 146 centers in Asia, Europe, and North America (December 2018-February 2024), enrolled 997 adults with human epidermal growth factor receptor 2-negative advanced GC/GEJC, randomized 1:1 to receive tislelizumab + chemotherapy or placebo + chemotherapy. The primary endpoint was overall survival (OS) in patients with PD-L1 Tumor Area Positivity (TAP) score ≥ 5% and the ITT population. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), safety, and tolerability. At 3-year follow-up, 959 (96.2%) patients had discontinued or completed treatment. The minimum follow-up duration was 36.6 months. RESULTS: In all randomized patients (n = 997), 69.4% male and 30.6% female, tislelizumab + chemotherapy improved OS versus placebo + chemotherapy [15.0 months (95% CI 13.6-16.5) vs. 12.9 months (95% CI 12.1-14.1); stratified hazard ratio (HR) 0.79]. Investigator-assessed PFS was also improved [6.9 months (95% CI 5.7-7.2) vs. 6.2 months (95% CI 5.6-6.9); stratified HR ...