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.
Current oncology reports. 2017 Feb [Epub]
Nizar M Tannir, Gisela Schwab, Viktor Grünwald
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1155 Pressler St., Unit 1374, Houston, TX, 77030, USA., Exelixis, Inc., 210 E. Grand Avenue, South San Francisco, CA, 94080, USA. ., Departments of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Medical School Hannover (MHH), OE6860 Carl-Neuberg-Str. 1, 30625, Hannover, Germany.