Angiogenic and immunomodulatory biomarkers in axitinib-treated patients with advanced renal cell carcinoma

Future Oncol. 2020 Jun;16(17):1199-1210. doi: 10.2217/fon-2020-0212. Epub 2020 May 4.

Abstract

Aim: Immunomodulatory mechanisms contributing to angiogenic inhibition in renal tumors are not well characterized. We report associations between efficacy and tumor-associated immune cells and mRNA/miRNA expression in patients from AXIS. Materials & methods: Immunohistochemistry (n = 52) and mRNA/miRNA expression analyses (n = 72) were performed on tumor samples. Results: In axitinib-treated patients, higher CXCR4 and TLR3 expression, respectively, was associated with longer progression-free survival (hazard ratio; 95% CI: 0.3; 0.1-0.8 and 0.4; 0.2-0.9) and showed interaction with treatment (p = 0.029 and p < 0.001); lower CCR7 expression was associated with objective response (odds ratio: 0.1; 95% CI: 0.01-1.0) and longer overall survival (hazard ratio: 3.9; 95% CI: 1.4-10.3). Conclusion: CCR7, CXCR4 and TLR3 expression levels may be prognostic/predictive of clinical benefit with axitinib. Clinical trial identifier: ClinicalTrials.gov NCT00678392.

Keywords: axitinib; biomarker; renal cell carcinoma; sorafenib; survival; tumor response.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Axitinib / pharmacology*
  • Axitinib / therapeutic use
  • Biomarkers*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / etiology*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology*
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Immunomodulation / drug effects*
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / etiology*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • MicroRNAs / genetics
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / immunology*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Biomarkers
  • MicroRNAs
  • Protein Kinase Inhibitors
  • Axitinib

Associated data

  • ClinicalTrials.gov/NCT00678392