Antibiotic Use and Survival in Patients With Late-Stage NSCLC Treated With Chemoimmunotherapy

Abstract

Introduction: Immunotherapy has improved survival in patients with advanced 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 chemoimmunotherapy, drawn from the Surveillance, Epidemiology, and End Results-Medicare data set. 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 analyses were performed using SAS. Results: The study included 788 patients, 440 (56%) of whom received antibiotics within 2 months before 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 1 round of antibiotics versus zero or 1 round (p < 0.0001). After adjustment, receipt of antibiotics (hazard ratio [HR]adj: 1.17, 95% confidence interval [CI]: 0.99–1.37) and receipt of multiple rounds of antibiotics (HRadj: 1.35, 95% CI: 1.14–1.60) were statistically significantly associated with worse survival. Among just those receiving chemoimmunotherapy (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). Conclusions: Antibiotic use concurrent with chemoimmunotherapy seems to be associated with worse survival. This is more pronounced when more cycles of antibiotics are given. IRB approval number: STUDY-19-00500.

Keywords

• Immunotherapy
• Chemoimmunotherapy
• Immune checkpoint inhibitors
• Antibiotics
• NSCLC
• Survival