Association of Antibiotic Exposure with Survival Outcomes in Patients with Advanced KRAS-Mutated NSCLC Receiving Immune Checkpoint Inhibitors

Background: Antibiotic exposure has been associated with reduced benefit from immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). However, evidence in patients with KRAS-mutated NSCLC remains limited. This study evaluated the associations of antibiotic and probiotic exposure with survival outcomes in patients with advanced KRAS-mutated NSCLC receiving ICIs. Methods: This multicenter retrospective study included patients with advanced KRAS-mutated NSCLC who received at least one dose of ICI-based therapy. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate factors associated with survival outcomes. Results: A total of 101 patients were included, of whom 23 were exposed to antibiotics and 18 received probiotics. All patients had documented KRAS mutations. Eight patients received KRAS-targeted inhibitors after ICI progression, and none received KRAS-targeted inhibitors before or during ICI treatment. The median PFS was 9.0 months in the antibiotic-exposed group and 14.4 months in the non-antibiotic group (p = 0.041). The median OS was 23.5 and 38.4 months, respectively (p = 0.017). After multivariable adjustment, antibiotic exposure remained associated with shorter PFS (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.08–3.84; p = 0.029) and OS (HR, 2.85; 95% CI, 1.30–6.22; p = 0.009). Probiotic exposure was not significantly associated with PFS or OS. Conclusions: Antibiotic exposure was associated with shorter PFS and OS in patients with advanced KRAS-mutated NSCLC receiving ICIs, whereas probiotic exposure was not significantly associated with survival outcomes.