First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-305

作者：Markus Moehler, Do‐Youn Oh, Ken Kato, Hendrik‐Tobias Arkenau, Josep Tabernero, Keun‐Wook Lee, Sun Young Rha, Hidekazu Hirano, David R. Spigel, Kensei Yamaguchi, Lucjan Wyrwicz, Umut Dişel, Roberto Pazo-Cid, Lorenzo Fornaro, Yaling Xu, Tao Sheng, Silu Yang, Alysha Kadva, Marcia Cruz‐Correa, Rui‐Hua Xu · 发表于：Advances in Therapy · 年份：2025 · DOI：10.1007/s12325-025-03133-7 · 被引用次数：9 · 研究领域：Cancer Immunotherapy and Biomarkers、Gastric Cancer Management and Outcomes、Protein Degradation and Inhibitors

INTRODUCTION: Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score < 1 or TAP score < 1%, due to an unfavorable benefit-risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%. METHODS: Adult patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC were randomized to tislelizumab 200 mg or placebo with ICC every 3 weeks. Efficacy and safety outcomes of tislelizumab plus ICC versus placebo plus ICC were retrospectively assessed in those with a PD-L1 TAP score ≥ 1%. RESULTS: At the final analysis cutoff (February 28, 2023), 432 patients received tislelizumab plus ICC and 453 received placebo plus ICC, and had a PD-L1 TAP score ≥ 1%. Clinically meaningful improvements to OS were observed with tislelizumab plus ICC compared with placebo plu...