Antibiotic Use and Survival in Late-Stage Non-Small Cell Lung Cancer Patients Treated with Chemo-Immunotherapy

Introduction Immunotherapy has improved survival in patients with advanced non-small cell lung cancer (NSCLC). Efficacy may decrease when patients are treated with antibiotics, possibly due to gut microbiome disruption, but few studies have investigated this using real-world, patient-level populations in the United States. Methods We have analyzed antibiotic use in patients with stage IV first, primary NSCLC diagnosed in 2015 and treated with chemotherapy or chemo-immunotherapy, drawn from the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset. Patients had to have continuous Part A, Part B and Part D Medicare coverage. Survival was determined through Kaplan-Meier and Cox Proportional Hazards models. All data analysis was performed using SAS. Results The study included 788 patients, 440 (56%) of whom received antibiotics within two months prior or after starting systemic treatment. The median follow-up time was 11.64 months. There was a statistically significant difference in survival for patients who received antibiotics (p = 0.007), and who had more than one round of antibiotics vs zero or 1 round (p = <0.0001). After adjustment, receipt of antibiotics (HRadj: 1.17, 95% CI: 0.99-1.37), and receipt of multiple rounds of antibiotics (HRadj: 1.35, 95% CI: 1.14-1.60) was statistically significantly associated with worse survival. Among just those receiving chemo-immunotherapy (n=203; 26%), there was still an increased risk of death for those receiving multiple antibiotic rounds (HRadj: 1.52, 95% CI: 1.09-2.13). Conclusion Antibiotic use concurrent with chemo-immunotherapy appears to be associated with worse survival. This is more pronounced when more cycles of antibiotics are given.