Association of antibiotic exposure with the mortality in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy: A hospital-based retrospective cohort study

Background: Preclinical studies showed that antibiotic exposure played a role in clinical outcomes in patients with chemotherapy via modulation of microbiota. However, it remains unknown whether antibiotic exposure during the bevacizumab therapy affects the clinical outcomes in metastatic colorectal cancer(mCRC) patients. This study aimed to examine the association between the antibiotic medication and the clinical outcomes in mCRC patients with bevacizumab therapy. Methods: This retrospective cohort analysis included 147 mCRC patients treated with bevacizumab. The hazard ratio of death was estimated using three Cox proportional hazards models with (1) never vs ever; (2) never vs 1–6 days and 7–40 days;(3) increase per day, and further tested using propensity score matching (PSM) and landmark analysis. A smooth curve technique was used to explore the shape of dose-response relationship. Results: Compared with the non-antibiotic group, antibiotic exposure was inversely associated with the mortality in the antibiotic group after adjustment for demographic and other potential confounders (a history of medication: HR, 0.650(95%CI: 0.360 to 1.173); an increase per day: HR, 0.967(CI: 0.924 to 1.011); 1–6 days: HR, 0.859(CI: 0.441 to 1.674); 7–40 days: HR, 0.474(CI: 0.225 to 0.999); P for trend = 0.040). A test for the interaction between sex was statistically significant (p = 0.016). A similar result was found as measured by landmark and PSM analysis. Significant negative dose-response relationship was shown by smooth curve analysis in the male patients but not female after adjustment for confounders(p = 0.028). No association was found between the antibiotic medication and adverse events of bevacizumab. Conclusion: Antibiotic exposure could be inversely associated with the mortality in mCRC patients treated with bevacizumab.