Clinical characteristics and prognostic outcomes in KRAS-mutant non-small cell lung cancer: A real-world study with or without COPD comorbidity.

[BACKGROUND] Chronic obstructive pulmonary disease (COPD) is the most prevalent comorbidity among lung cancer patients, but its clinical and prognostic relationship with KRAS-mutant non-small cell lung cancer (NSCLC) remains unclear.

[METHODS] This multicenter retrospective cohort study enrolled 163 histologically confirmed KRAS-mutant NSCLC patients, including 59 with COPD and 104 without COPD. Clinical data consisted of baseline characteristics, co-mutation profiles, and survival outcomes were collected and efficacy evaluations. PFS and OS were compared using the Kaplan-Meier method and log-rank test.

[RESULTS] The COPD-LC group showed with a higher proportion of KRAS G12C mutations (47.4% vs. 26.2%, P = 0.028) and higher smoking rates (91.5% vs. 65.4%, P <0.001). Additionally, this group had a poorer baseline performance status and a higher Charlson Comorbidity Index. Chemoimmunotherapy significantly improved survival in advanced-stage NSCLC patients (mPFS: 9 vs. 6 months, HR = 0.62, P = 0.022; mOS: 24 vs. 11 months, HR = 0.53, P = 0.023), particularly those with COPD-comorbid lung cancer. Notably, within the COPD-LC subgroup, KRAS G12C-mutant patients achieved significantly longer median PFS compared to non-G12C subtypes (11.5 vs. 5 months, HR = 0.38, P = 0.009) and no significant differences in mPFS or mOS were observed between PS 0-1 and PS 2-3 groups. Co-mutations were identified in 78.6% of patients, with no significant intergroup differences.

[CONCLUSION] COPD-comorbid KRAS-mutant NSCLC patients exhibit unique G12C subtype enrichment and distinct clinical features. Chemoimmunotherapy represents an effective first-line strategy for this population, particularly benefiting those with G12C mutations.