Antibiotic administration shortly before or after immunotherapy initiation is correlated with poor prognosis in solid cancer patients: An up-to-date systematic review and meta-analysis.

Objective: Immune checkpoint inhibitors (ICIs) have recently achieved inspiring performance in improving the prognosis of various solid tumors. Gut microbiome plays a crucial modulatory role in the efficacy of ICIs, which can be influenced by antibiotic (ATB) administration. In this meta-analysis, we aimed to clarify the correlations of ATB administration with the prognosis of solid cancer patients receiving ICI treatment.

Method: The eligible literatures were searched using PubMed, Cochrane Library, Web of Science, and Clinical trials.gov databases before 29 February 2020. The correlations of ATB administration with overall survival (OS) and progression-free survival (PFS) were determined using Hazard ratios (HRs) coupled with 95% confidence intervals (CIs).

Results: A total of 33 studies enrolling 5565 solid cancer patients receiving ICI treatment were included in this meta-analysis. As a whole, ATB administration was significantly correlated worse OS (HR = 1.76, 95%CI = 1.41-2.19, P < 0.00001) and PFS (HR = 1.76, 95%CI = 1.47-2.12, P < 0.00001). This significant association was then observed in the subgroup analysis based on region (except for OS in Europe), sample size, age, therapeutic strategy and ICI type. The similar results were also found in subgroup analysis for lung, renal cell (except for OS) and other cancers (such as melanoma) but not for mixed cancers. In addition, the ICI efficacy was more likely to be diminished by ATB administration within a time frame from 60 days before to 60 days after ICI initiation.

Conclusion: ATBs should be used cautiously in solid cancer patients receiving ICIs. However, further validations are still essential due to existing publication bias.