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

Abstract

This study aimed to characterize the genomic landscape of Korean gastric cancer and evaluate associations among oncogenic alterations, established biomarkers, demographics, and treatment outcomes. 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. Among 1,283 patients (median [IQR] age, 61 [52-68] years; 827 males [64.46%]), <i>TP53</i> (51.91%), <i>ARID1A</i> (19.02%), <i>ERBB2</i> (12%), <i>KRAS</i> (10.29%), and <i>PIK3CA</i> (9.12%) were the most frequently altered genes. Epstein-Barr virus-positive tumors exhibited enrichment of <i>BCOR</i>, <i>PIK3CA</i>, and <i>ARID1A</i> alterations and reduced <i>TP53</i> mutations (false discovery rate [FDR] adjusted <i>P</i> < .01). Human epidermal growth factor receptor 2-positive tumors were characterized by coamplification of <i>ERBB2</i>, <i>CCNE1</i>, and <i>MYC</i> (FDR adjusted <i>P</i> < .001), whereas PD-L1 positivity was associated with <i>KRAS</i> and <i>CDKN2A</i> alterations (FDR-adjusted <i>P</i> < .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 (<i>v</i> the low TMB subgroup; hazard ratio [HR], 0.48 [95% CI, 0.25 to 0.93]; <i>P</i> = .03), particularly when combined with PD-L1 positivity (<i>v</i> all other biomarker-defined subgroups; HR, 0.33 [95% CI, 0.14 to 0.76]; <i>P</i> = .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, <i>FGFR2</i> and <i>MET</i> alterations were linked to poorer outcomes, whereas <i>PIK3CA</i> mutations were observed in patients with longer overall survival after first-line chemotherapy. 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.