Patient-Level KRAS G12C Prevalence Among Hispanic/Latino and Non-Hispanic White Patients in Real-World Clinicogenomic Cohorts

KRAS G12C is a treatment-defining biomarker in non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD). Hispanic/Latino (H/L) patients remain undercharacterized in precision oncology datasets, and patient-level KRAS G12C prevalence has not been consistently quantified using strict ethnicity definitions. We analyzed MSK-CHORD and AACR GENIE after excluding the MSK contributing center. H/L required explicit Hispanic/Latino-origin annotation; non-Hispanic White (NH-W) required White race with explicit non-Hispanic ethnicity. Primary analyses compared patient-level KRAS G12C prevalence in mutually exclusive LUAD and non-LUAD NSCLC. In LUAD, KRAS G12C prevalence was lower in H/L than NH-W patients in MSK-CHORD (7.9% vs 15.4%; OR, 0.47; 95% CI, 0.30-0.74; P<0.001) and GENIE (7.2% vs 15.1%; OR, 0.44; 95% CI, 0.33-0.58; P<0.0001). In non-LUAD NSCLC, differences were smaller and not significant in MSK-CHORD (4.8% vs 5.1%; OR, 0.94; P=1.000) or GENIE (4.9% vs 6.7%; OR, 0.73; P=0.461). In MSK-CHORD LUAD, adjustment for smoking moved the OR from 0.50 to 0.68. H/L patients had lower patient-level KRAS G12C prevalence than NH-W patients in LUAD across two real-world clinicogenomic cohorts. The finding was histology-specific and attenuated after smoking adjustment, supporting a biomarker-yield interpretation.