title: Cabozantinib: an Active Novel Multikinase Inhibitor in Renal Cell Carcinoma.
abstract: 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.
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1155 Pressler St., Unit 1374, Houston, TX, 77030, USA.
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.affiliation: Exelixis, Inc., 210 E. Grand Avenue, South San Francisco, CA, 94080, USA. gschwab@exelixis.com.
authors.forename: Gisela
authors.initials: G
authors.lastname: Schwab
authors.affiliation: Departments of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Medical School Hannover (MHH), OE6860 Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
mesh_terms: D000813:Anilides / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068338:Everolimus / Q000627:therapeutic use; D006801:Humans; D000077594:Nivolumab; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D020123:Sirolimus / Q000627:therapeutic use; D057170:Translational Research, Biomedical; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D000813:Anilides; D000911:Antibodies, Monoclonal; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011804:Quinolines; C558660:cabozantinib; D000077594:Nivolumab; D000068338:Everolimus; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D040262:Receptors, Vascular Endothelial Growth Factor; C497446:VHL protein, human; C531958:lenvatinib; D020123:Sirolimus
keywords: AXL; Angiogenesis; Cabozantinib; MET; RCC; Renal cell carcinoma; VEGF receptor