The impact of antibiotics on efficacy of immune checkpoint inhibitors in malignancies: A study based on 44 cohorts.

BACKGROUND Pre-clinical and clinical data had revealed the gut microbiome plays a critical role in immune checkpoint inhibitors (ICIs) efficacy. This study was designed to investigate whether antibiotics (ATBs) affect the prognosis of malignancies treated with ICIs. METHODS Electronic databases were searched to identify relevant trials that evaluated the impact of ATBs on ICIs efficacy. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by HRs with corresponding 95%CIs. Subgroup analyses were performed based on cancer type, study design, ICIs agent, and time of ATBs administration. RESULTS Totally, 12,492 individuals in the 44 cohorts were recruited. Pooled results showed that ATBs administration was significantly correlated with a worse objective remission rate (ORR) (OR = 0.61, 95%CI (0.42-0.90), P = 0.0128), PFS (HR = 1.18, 95%CI (1.11-1.25), P < 0.0001), and OS (HR = 1.20, 95%CI (1.15-1.25), P < 0.0001) in patients treated with ICIs. In subgroup analyses, patients treated with ICIs exposed to ATBs suffered an evidently worse ORR in arms of renal cell carcinoma (RCC) (OR = 0.30, 95%CI (0.14-0.67), P = 0.0034), multiple (OR = 0.44, 95%CI (0.27-0.73), P = 0.0016), and before ICIs initiation (OR = 0.47, 95%CI (0.32-0.71), P = 0.0003) without heterogeneity; experienced a worse PFS and OS in arms of non-small cell lung cancer, melanoma, RCC, urothelial carcinoma, multiple, prospective, retrospective, PD-(L)1 alone, PD-(L)1 plus CTLA-4, before ICIs initiation, before ICIs initiation and concurrent, and before or after ICIs within 1 month, while a better PFS and OS in concurrent with ICIs arm. CONCLUSIONS ATBs administration was negatively associated with ORR, PFS and OS in malignancies treated with ICIs, while the time of ATBs exposure might impact ICIs efficacy.