Introduction Immune checkpoint inhibitors targeting programmed cell death protein-(ligand) 1 (PD-[L]1) have transformed first-line treatment of advanced gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, important regional differences in epidemiology, tumor biology, clinical presentation and treatment practices between Asian and non-Asian populations have raised questions regarding the global generalizability of chemoimmunotherapy outcomes.
Introduction
Immune checkpoint inhibitors targeting programmed cell death protein-(ligand) 1 (PD-[L]1) have transformed first-line treatment of advanced gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, important regional differences in epidemiology, tumor biology, clinical presentation and treatment practices between Asian and non-Asian populations have raised questions regarding the global generalizability of chemoimmunotherapy outcomes.
Problem Statement
Although PD-(L)1 inhibitors combined with chemotherapy are widely incorporated into treatment guidelines, uncertainty persists regarding whether survival benefits differ between Asian and non-Asian patients with advanced GC/GEJC. Clarifying these regional outcomes is critical for global treatment standardization, regulatory decision-making and equitable access to immunotherapy.
Summary
This large meta-analysis of phase III randomized trials demonstrates that first-line PD-(L)1 inhibitors combined with chemotherapy significantly improve overall survival and progression-free survival in advanced HER2-negative GC/GEJC irrespective of Asian or non-Asian regional background. Across more than 6700 patients, survival benefits were remarkably consistent between geographic populations, supporting the broad applicability of chemoimmunotherapy across diverse clinical settings. Although progression-free survival appeared numerically more favorable in Asian populations, the difference was not statistically significant and may partly reflect variations in disease burden and patterns of recurrent versus de novo metastatic disease at study entry. Importantly, treatment-related adverse events remained comparable between immunotherapy-based regimens and chemotherapy-alone controls, reinforcing the acceptable safety profile of combined checkpoint inhibition. The findings also support the concept that immunotherapy benefit in advanced GC/GEJC is primarily biology-driven rather than geography-driven. Sensitivity analyses excluding negative studies and PD-L1–enriched cohorts did not materially alter outcomes, strengthening the robustness of the conclusions. The review further highlights persistent limitations in current evidence, including inconsistent reporting of biomarker-defined subgroups, regional genomic differences and immune-related adverse events. Overall, this study provides strong evidence supporting global use of first-line PD-(L)1 inhibitor plus chemotherapy strategies in advanced gastric and gastroesophageal junction adenocarcinoma and may help reduce disparities in worldwide access to modern immunotherapy.
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