Ther Adv Gastroenterol. 2026 May 15;19:17562848261446862. doi: 10.1177/17562848261446862. eCollection 2026.
ABSTRACT
BACKGROUND: ARID1A mutations are frequent in gastric cancer (GC) and may indicate an immune-active tumor microenvironment.
OBJECTIVES: This study aimed to assess the efficacy of the immune checkpoint inhibitor (ICI) plus chemotherapy as first-line therapy in advanced GC and explore its association with key molecular features according to the status of ARID1A-mutation.
DESIGN: This was a retrospective, single-center cohort study.
METHODS: We analyzed 258 patients with advanced HER2-negative GC who received ICI plus chemotherapy between 2022 and 2024. ARID1A mutation status and other molecular features were assessed using next-generation sequencing. Also, the status for Epstein-Barr virus (EBV), programmed death-ligand 1 (PD-L1), and claudin 18.2 was done. Treatment outcomes were evaluated between ARID1A-mutant and wild-type groups.
RESULTS: Among 258 patients, 67 (26.0%) harbored at least one ARID1A mutation. ARID1A mutant tumors (MT) showed significantly higher tumor mutational burden (median 18.0 vs 6.7 mut/Mb), EBV positivity (11.8% vs 0.6%), MSI-H status (10.6% vs 6.3%), and PD-L1 CPS ⩾50 (14.9% vs 1.0%) compared to wild-type (WT). The median progression-free survival (PFS) was numerically longer in the ARID1A MT group (9.7 vs 8.5 months; HR 0.75; 95% CI, 0.53-1.10), though not statistically significant. There was no significant difference for the ORR (55.2% vs 64.4%, p = 0.19), and the overall survival (27.4 vs 31.1 months; HR 0.83; 95% CI, 0.58-1.20) between the two groups.
CONCLUSION: ARID1A mutations were associated with immune-active molecular features and a trend toward improved PFS to ICI plus chemotherapy. Further research for ARID1A as a potential biomarker for ICI is warranted in advanced GC.
PMID:42153215 | PMC:PMC13180195 | DOI:10.1177/17562848261446862
