AbstractPurposeThe relationship between mutant KRAS and the risk of disease progression and death in advanced non‐squamous non‐small cell lung cancer (NSCLC) is still controversial among current studies, and the effects of distinct KRAS mutations on prognosis may be different. This study aimed to further investigate the association between them.Patients and MethodsOf the 184 patients eventually included in the study, 108 had KRAS wild type (WT) and 76 had KRAS mutant type (MT). Kaplan–Meier curves were plotted to describe the survival for patients among groups, while log‐rank tests were conducted to evaluate the survival differences. The univariate and multivariate Cox regression were performed to identify predictors, and subgroup analysis was used to verify the interaction effect.ResultsSimilar efficacy of first‐line therapy was observed for KRAS MT and WT patients (p= 0.830). The association between KRAS mutation and progression‐free survival (PFS) was not significant in univariate analysis (hazard ratio [HR] = 0.94; 95% CI, 0.66–1.35), and no KRAS mutation subtype significantly affected PFS. However, KRAS mutation and KRAS non‐G12C were associated with increased risk of death compared to KRAS WT in univariate and multivariate analysis. Univariate and multivariate analysis also confirmed that chemotherapy combined with antiangiogenesis or immunotherapy in the KRAS mutation group was associated with decreased risk of disease progression. However, the overall survival (OS) among KRAS mutant patients received different first‐line treatments did not significantly differ.ConclusionKRAS mutations and their subtypes are not independent negative predictors of PFS, while KRAS mutation and KRAS non‐G12C were independent prognostic factors for OS. Chemotherapy combined with antiangiogenesis or immunotherapy conferred decreased risk of disease progression to KRAS mutation patients compared to single chemotherapy.