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

Clin Genitourin Cancer. 2018 Oct;16(5):365-368. doi: 10.1016/j.clgc.2018.05.001. Epub 2018 May 29.

Abstract

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.

Keywords: Antibiotics; Pazopanib; Sunitinib; VEGF-TKI.

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Bacteroides / drug effects*
  • Carcinoma, Renal Cell / drug therapy*
  • Feces / microbiology*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Anti-Bacterial Agents
  • Protein Kinase Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A