Abstract
Background: Programmed death-1 (PD-1) inhibitors have advanced treatment of patients with non–small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, and other cancers. Lung cancer is commonly diagnosed at the advanced stage in an older adult patient population; therefore, many contributing factors can influence the treatment response. Not all patients respond to PD-1 treatment and even less is known for aging patients with comorbidities, altered gut microbiome, and multiple concomitant medications. Objective: This study aimed to evaluate overall survival (OS) in older adult patients with lung cancer receiving PD-1 inhibitors and medications known to affect the gut microbiome. Methods: Surveillance, Epidemiology, and End Results–Medicare is a database that links tumor registry data with Medicare enrollment and claims files. The study cohort was determined based on lung cancer histology, claims for nivolumab or pembrolizumab, and continuous enrollment. Oral antibiotic (Ab) claims were identified in the Part D file and assigned to 14-, 30-, or 60-day comparison groups. Patient characteristics between PD-1 and Ab exposure at 14, 30, and 60 days were assessed by chi-square test. The association between OS and Ab was analyzed using the Cox proportional hazards model and Kaplan-Meier curves. Results: We identified 3445 patients who had lung cancer and received PD-1 inhibitors from 2014 to 2017. Of those patients, 1702 (49%) received an oral Ab within 60 days of starting the PD-1 therapy. Ab use during the initiation of PD-1 treatment was associated with shorter OS when given within 60 days of initiation of treatment (hazard ratio 1.273 [95% confidence interval 1.104–1.469], P = 0.0009) than patients with no Ab claim within 180 days of index. Conclusion: Utilization of immunotherapy is increasing in the Medicare population and these patients commonly have age-related changes to the immune systems and microbiome. These results provide OS estimates for older adult patients with lung cancer treated with PD-1 and receiving medications known to alter important gut microbiome diversity. The complex interactions of the immune system, microbiome, and immunotherapy response are key for the effective treatment of patients with NSCLC.