Real-World Genomic Landscape of Korean Gastric Cancer: Integrating Biomarker Associations and Clinical Outcomes in Metastatic Gastric Cancer.

PURPOSE: This study aimed to characterize the genomic landscape of Korean gastric cancer and evaluate associations among oncogenic alterations, established biomarkers, demographics, and treatment outcomes.

METHODS

A total of 1,283 patients with gastric cancer who underwent tumor-only targeted sequencing as part of practice and received palliative treatment between January 2017 and August 2025 at the Samsung Medical Center were included.

RESULTS

Among 1,283 patients (median [IQR] age, 61 [52-68] years; 827 males [64.46%]), TP53 (51.91%), ARID1A (19.02%), ERBB2 (12%), KRAS (10.29%), and PIK3CA (9.12%) were the most frequently altered genes. Epstein-Barr virus-positive tumors exhibited enrichment of BCOR, PIK3CA, and ARID1A alterations and reduced TP53 mutations (false discovery rate [FDR] adjusted P < .01). Human epidermal growth factor receptor 2-positive tumors were characterized by coamplification of ERBB2, CCNE1, and MYC (FDR adjusted P < .001), whereas PD-L1 positivity was associated with KRAS and CDKN2A alterations (FDR-adjusted P < .05). Among patients treated with first-line nivolumab plus chemotherapy (n = 269), those with high tumor mutational burden (TMB; ≥10 mutations per megabase) had improved overall survival (v the low TMB subgroup; hazard ratio [HR], 0.48 [95% CI, 0.25 to 0.93]; P = .03), particularly when combined with PD-L1 positivity (v all other biomarker-defined subgroups; HR, 0.33 [95% CI, 0.14 to 0.76]; P = .006). Moreover, as TMB levels increased, patients derived greater survival benefit from nivolumab plus chemotherapy versus chemotherapy alone, even among those with microsatellite-stable tumors. Across treatment regimens, FGFR2 and MET alterations were linked to poorer outcomes, whereas PIK3CA mutations were observed in patients with longer overall survival after first-line chemotherapy.

CONCLUSION

Our findings provide a comprehensive genomic landscape of Korean gastric cancer and underscore the clinical relevance of integrating genomic and established biomarkers to advance precision oncology.