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

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.

• Authors: Danielle A Murphy, Brian I Rini, Bernard Escudier, Robert J Motzer, Panpan Wang, Sherry Li, J Andrew Williams, Jamal C Tarazi, Jean-Francois Martini
• Journal: Future oncology (London, England) (Future Oncol) Vol. 16 Issue 17 Pg. 1199-1210 (Jun 2020) ISSN: 1744-8301 [Electronic] England
• PMID: 32363929 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Biomarkers
• MicroRNAs
• Protein Kinase Inhibitors
• Axitinib

Topics

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