Effects of antibiotics on the anti-tumor efficacy of immune checkpoint inhibitor therapy.

Abstract

Purpose: Immunotherapy using immune checkpoint inhibitors (ICIs) has shown several benefits over traditional therapies. However, the eligible population remains small. Antibiotic (ATB) use might reduce immunotherapy efficacy by disrupting the gut microbiota. However, in China, ATB effect on ICI therapy efficacy remains unelucidated. We aimed to assess the effects of ATBs on the anti-tumor efficacy of ICIs to provide a reference for clinical use.

Methods: We included 134 patients with advanced tumors undergoing ICI therapy at Shanghai Jiading District Central Hospital from January 1, 2021, to October 1, 2023. They were divided into Non-ATB and ATB groups based on ATB use within 30 days before and after ICI administration. Moreover, we compared progression-free (PFS) and overall (OS) survival between the groups.

Results: Median PFS and OS were lower in the ATB than in the Non-ATB group (PFS: 4.0 vs. 5.5 months; OS: 5.4 vs. 6.5 months). Univariate analysis revealed that ATB use significantly affected PFS (hazard ratio [HR] = 2.318, 95% confidence interval [CI] = 1.281-4.194, P = 0.005) and OS (HR = 2.115, 95% CI = 1.161-3.850, P = 0.014). Moreover, multivariate analysis revealed poor PFS (HR = 2.573, 95% CI = 1.373-4.826, P = 0.003) and OS (HR = 2.452, 95% CI = 1.298-4.632, P = 0.006) in patients who received ATBs during ICI therapy.

Conclusions: ATB use is negatively correlated with ICI therapy efficacy, leading to reduced PFS and OS in patients undergoing such treatment. Owing to the significant impact of ATBs on the human gut microbiome, regulation of the gut microbiome may emerge as a novel therapeutic target that can enhance the clinical activity of ICIs.