Impact of antibiotic exposure on survival outcomes in NSCLC patients treated with third-generation EGFR-TKIs

Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the recommended first-line therapy for advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, the impact of antibiotic exposure prior to initiating third-generation EGFR-TKIs on treatment efficacy and survival outcomes remains unclear. Patients with NSCLC who received third-generation EGFR-TKIs at West China Hospital of Sichuan University between January 2017 and November 2024 were retrospectively identified from electronic medical records. Antibiotic exposure was defined as any antibiotic prescription within 60 days prior to TKIs initiation. Patients were matched using propensity scores to reduce differences in baseline characteristics between the antibiotic and non-antibiotic groups. Multivariable Cox models were performed to evaluate the association between antibiotic exposure and progression-free survival (PFS) and overall survival (OS). After propensity score matching, 64 patients remained in the matched antibiotic group, and 156 in the matched non-antibiotic group. Patients in the antibiotic group had significantly shorter median PFS (16.2 vs. 22.4 months; P = 0.001) and OS (38.1 vs. 62.9 months; P = 0.003) compared with those in the non-antibiotic group. After multivariable adjustment, antibiotic exposure remained an independent predictor of worse PFS (HR 1.625; 95% CI, 1.152 to 2.291; P = 0.006) and OS (HR 1.801; 95% CI, 1.130 to 2.868; P = 0.013). Prior antibiotic exposure was associated with poorer survival outcomes in NSCLC patients receiving third-generation EGFR-TKIs. Further larger prospective studies are needed to confirm these findings.