Cabozantinib: an Active Novel Multikinase Inhibitor in Renal Cell Carcinoma

• Published in: Current Oncology Reports Vol. 19; no. 2; p. 14
• Main Authors: Tannir, Nizar M., Schwab, Gisela, Grünwald, Viktor
• Format: Journal Article Book Review
• Language: English
• Published: New York Springer US 01.02.2017; Springer Nature B.V
• Subjects: Anilides - therapeutic use; Antibodies, Monoclonal - therapeutic use; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Everolimus - therapeutic use; Evolving Therapies (R Bukowski; Evolving Therapies (R Bukowski, Section Editor); Humans; Medicine; Medicine & Public Health; Oncology; Phenylurea Compounds - therapeutic use; Protein Kinase Inhibitors - therapeutic use; Pyridines - therapeutic use; Quinolines - therapeutic use; Receptors, Vascular Endothelial Growth Factor - genetics; Section Editor; Sirolimus - therapeutic use; Topical Collection on Evolving Therapies; Translational Medical Research; Von Hippel-Lindau Tumor Suppressor Protein - genetics; Angiogenesis; Cabozantinib; RCC; Renal cell carcinoma; AXL; VEGF receptor; MET
• ISSN: 1523-3790; 1534-6269
• DOI: 10.1007/s11912-017-0566-9

Clear cell renal cell carcinoma (RCC) is characterized by inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL loss drives tumor angiogenesis and accounts for the clinical activity of VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), the first-line standard of care for advanced RCC. Within the last year, three new second-line treatments have received FDA approval for use after anti-angiogenic therapy: the immune checkpoint inhibitor nivolumab, the TKI cabozantinib, and the combination of the TKI lenvatinib and the mTOR inhibitor everolimus. Cabozantinib inhibits VEGFRs, MET, and AXL, kinases that promote tumorigenesis, angiogenesis, metastasis, and drug resistance. Compared with everolimus, cabozantinib has shown statistically significant improvements in the three key efficacy endpoints of overall survival, progression-free survival, and objective response rate in patients with RCC who were previously treated with a VEGFR TKI. Herein, we summarize the translational research and clinical development that led to approval of cabozantinib as second-line therapy in RCC.