Antibiotics and outcomes of cancer immunotherapy: An updated meta-analysis and clinical applications.

Abstract

The gut microbiome is a modifiable determinant of response to immune checkpoint inhibitors (ICI), positioning antibiotic exposure as a critical yet under-recognized risk factor for worse survival outcomes in immuno-oncology. As nearly 30% of ICI-treated patients receive antibiotics and indications of cancer immunotherapy are expanding, this issue represents a global challenge in oncology. Here, we paint an updated and comprehensive landscape of antibiotic exposure in immuno-oncology, provide actionable clinical recommendations, and envision future avenues for improvement. First, we describe the biological mechanisms by which antibiotic-induced dysbiosis contributes to ICI resistance. Next, through an updated meta-analysis of 116 cohorts and 97,850 cancer patients treated with ICI, we found a significant association between antibiotic exposure and survival outcomes (overall survival, hazard ratio [HR]: 1.49, 95% confidence interval [CI]: 1.34-1.65; progression-free survival, HR: 1.44, 95% CI: 1.31-1.58). Finally, we discuss antibiotics stewardship and microbiome-centered strategies to prevent, diagnose, and/or repair dysbiosis.