title: Tivozanib for the treatment of renal cell carcinoma: results and implications of the TIVO-1 trial.
abstract: Multiple VEGF and mTOR inhibitors have provided improvements in median progression-free survival for metastatic renal cell carcinoma. Tivozanib is a potent and specific VEGFR-1, -2 and -3 tyrosine kinase inhibitor. Promising results led to the TIVO-I Phase III trial (n = 517) comparing tivozanib with sorafenib in patients who were either untreated or had received cytokines. This study met its primary end point by statistically significantly improving progression-free survival, but did impair overall survival, a secondary end point. Crossover from sorafenib to tivozanib may have confounded survival. Because of that detrimental survival, the US FDA rejected approval in May 2013, leading to interruption in its development for renal cell carcinoma.
authors.affiliation: University of Alabama, Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL, USA.
authors.forename: Amikumar
authors.initials: A
authors.lastname: Mehta
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018849:Controlled Clinical Trials as Topic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015337:Multicenter Studies as Topic; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C553176:tivozanib; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: TIVO-I trial; VEGFR 1, 2 and 3; metastatic renal cell carcinoma; tivozanib; tyrosine kinase inhibitor