Abstract
Objective: The prognostic and predictive significance of kirsten rat sarcoma viral oncogene homologue (KRAS) mutations in metastatic non-small cell lung cancer remains controversial, particularly in the immunotherapy era. Most previous studies compared KRAS-mutant tumors with heterogeneous KRAS wild-type populations that included other oncogenic driver alterations. This study aimed to evaluate the clinical impact of isolated KRAS mutations in patients with metastatic lung adenocarcinoma receiving first-line systemic therapy.
Material and Methods: This retrospective single-center study included patients with metastatic lung adenocarcinoma who underwent next-generation sequencing (NGS) between January 2023 and December 2025. Patients were categorized into two groups: those with isolated KRAS-mutant tumors and those with pan-wild tumors without any detectable oncogenic alterations on NGS. Patients with co-occurring oncogenic alterations were excluded. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression analysis.
Results: A total of 75 patients were included, comprising 28 with isolated KRAS mutations and 47 without detectable oncogenic alterations. Programmed death-ligand 1 expression ≥50% was significantly more frequent in the KRAS-mutant group (p=0.001). However, KRAS mutation status was not significantly associated with PFS or OS in either univariate or multivariate analyses. Median PFS was 10.77 months in the KRAS-mutant group and 7.84 months in the pan-wild group (p=0.597), while median OS was 18.97 months in the KRAS-mutant group and 18.27 months in the pan-wild group (p=0.926). Similarly, no significant differences in survival were observed between the immunotherapy-containing and chemotherapy-alone subgroups.
Conclusion: Isolated KRAS mutations were not associated with significantly different survival outcomes compared with tumors lacking detectable oncogenic alterations. These findings suggest that KRAS mutation status alone may have limited prognostic value in metastatic lung adenocarcinoma.