Antibiotic exposure windows and the efficacy of immune checkpoint blockers in patients with cancer: a meta-analysis.

Abstract

Immune checkpoint blockers (ICBs) improve the survival of patients with cancer, but primary or acquired drug resistance is inevitable. Intestinal microorganisms play an important role in immunotherapy and antitumor response, and antibiotic use can cause changes in intestinal microbial abundance and diversity. At present, the effects of antibiotic exposure on the anticancer activity of immunotherapy remain controversial. We performed a meta-analysis of relevant studies retrieved from electronic databases to assess the effects of the time window of antibiotic exposure on the efficacy of immune checkpoint inhibitors (ICIs). In accordance with the definition of antibiotic use in different articles, the time window of antibiotic exposure was divided into three groups, namely, Groups 1 (antibiotic use within 2 months before or after ICI), 2 (antibiotic use before ICI), and 3 (antibiotic use anytime during ICI). After retrieval from the PubMed and the Embase databases, 39 cohorts were included. In group 1, progression-free survival [PFS; hazard ratio (HR) =1.81, 95% confidence interval (CI): 1.40-2.34] and overall survival (OS; HR =1.81, 95% CI: 1.43-2.28) were prolonged in patients without antibiotic use. In group 2, the subgroup analysis showed that antibiotic use had no effect on PFS (HR =0.90, 95% CI: 0.65-1.26) and OS (HR =1.53, 95% CI: 0.89-2.62) when the exposure window defined as 0-3 months. In Group 3, pooled results indicated that PFS (HR =0.78, 95% CI: 0.65-0.93) was prolonged in patients with antibiotic during immunotherapy, and no difference was observed in the OS data (HR =0.98, 95% CI: 0.78-1.24) between the patients with antibiotic and without antibiotic. Antibiotic use in shortly time (within before or after 2 months) around the initiation of immunotherapy was remarkably related to the efficacy of ICIs. A different scenario could be observed that during the long-term treatment of ICIs, the effect of antibiotic exposure seems to be eliminated.