Targeting Bacteroides in Stool Microbiome and Response to Treatment With First-Line VEGF Tyrosine Kinase Inhibitors in Metastatic Renal-Cell Carcinoma

Vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) are a mainstay of treatment for metastatic renal-cell carcinoma. Stool microbiome composition is predictive of response to immunotherapy and cytotoxic chemotherapy. Antibiotics targeting Bacteroides species are associated with improved progression-free survival while receiving first-line VEGF-TKIs. Background: Vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs) are a mainstay of treatment for metastatic renal-cell carcinoma. Stool microbiome composition is predictive of response to immunotherapy and cytotoxic chemotherapy. We sought to investigate whether antibiotics targeting Bacteroides species affect progression-free survival (PFS) while receiving first-line VEGF-TKI therapy. Patients and Methods: Using a retrospective cohort of intermediate- and poor-risk metastatic renal-cell carcinoma patients from the University of Utah, we categorized patients receiving first-line VEGF-TKIs by receipt of antibiotics (Bacteroides spp., non-Bacteroides spp., or none) and assessed PFS by Kaplan-Meier and Cox proportional hazard models. Results: Of 145 patients, 17 received antibiotics with Bacteroides spp. coverage and 32 patients received antibiotics without Bacteroides spp. coverage. When compared to patients not receiving antibiotics, improved PFS was seen with each additional day antibiotics were prescribed with Bacteroides spp. coverage (hazard ratio = 0.92; 95% confidence interval, 0.83-0.99; P =.04). Conclusion: Targeting stool Bacteroides spp. with antibiotics improves PFS in patients receiving first-line VEGF-TKIs in a duration-dependent manner.