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. 2019 Sep 23;8(12):e1665973.
doi: 10.1080/2162402X.2019.1665973. eCollection 2019.

Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients

Xuan-Zhang Huang  1 , Peng Gao  1 , Yong-Xi Song  1 , Yan Xu  1 , Jing-Xu Sun  1 , Xiao-Wan Chen  1 , Jun-Hua Zhao  1 , Zhen-Ning Wang  1
Affiliations

Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients

Xuan-Zhang Huang et al. Oncoimmunology. .

Abstract

The gut microbiota plays a critical role in the anti-tumor immune response. There is increasing data showing that antibiotics (ATBs) change the composition of the gut microbiota and affect the efficacy of immune checkpoint inhibitors (ICIs). However, this is the first meta-analysis to evaluate the association between ATB use and ICI efficacy in cancer patients to provide a better understanding of the strength of this association. We performed a literature search for relevant studies that evaluated the relationship between ATB use and ICI efficacy using the PubMed, Embase, and conference databases. The primary outcomes consisted of overall survival (OS) and progression-free survival (PFS) measured by hazard ratios (HR) and corresponding 95% confidence intervals (CI). Subgroup and sensitivity analyses were also performed. A total of 19 eligible studies comprising 2,740 cancer patients treated with ICIs were included in the analysis. Our results indicated that ATB use was negatively associated with OS in cancer patients (HR = 2.37; 95% CI = 2.05-2.75; P < .001), without heterogeneity (I2 = 0.0%; P = .851). Moreover, ATB use significantly reduced PFS in patients treated with ICIs (HR = 1.84; 95% CI = 1.49-2.26; P < .001; I2 = 56.2%). Similar results were obtained in the subgroup analyses stratified by the time of ATB use and cancer type. Sensitivity analyses confirmed the stability of our results. Therefore, the findings of our meta-analysis indicated that ATB use is negatively associated with OS and PFS in cancer patients treated with ICI immunotherapy.

Keywords: Antibiotics; immune checkpoint inhibitors; immunotherapy; overall survival; progression-free survival.

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Figures

Figure 1.
Figure 1.
Literature search and study selection.
Figure 2.
Figure 2.
The associations between antibiotic use and overall survival (a) and progression-free survival (b) in cancer patients treated with immune checkpoint inhibitors.
Figure 3.
Figure 3.
Sensitivity analysis of overall survival (a) and progression-free survival (b) based on leave-one-out approach.
Figure 4.
Figure 4.
The associations between pre-therapy antibiotic use and overall survival (a) and progression-free survival (b) in cancer patients treated with immune checkpoint inhibitors.
Figure 5.
Figure 5.
Funnel plot of progression-free survival. A: overall analysis; B: sample size ≥ 100 subgroup.
See this image and copyright information in PMC

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