title: Tivozanib: status of development.
abstract: Tivozanib is a potent and highly specific orally available, tyrosine kinase inhibitor that targets vascular endothelial growth factor (VEGF) receptor-1, VEGF receptor-2, and VEGF receptor-3 at very low concentrations with a long half-life (4 days). After its promising activity in xenograft and preclinical models, tivozanib was evaluated in early phase clinical trials in various solid tumors. The phase III trial (TIVO-1) compared tivozanib with sorafenib in metastatic clear cell renal cell carcinoma (RCC). Because of detrimental overall survival (OS), Oncology Drug Advisory Committee (ODAC) voted against its approval in RCC. Tivozanib is also being evaluated in various other solid tumors like breast, gastrointestinal cancers, hepatocellular cancer, sarcomas, and gynecological cancer. In BATON-CRC trial, low-serum neuropilin-1 (NRP-1) levels were associated with better progression-free survival (PFS) in patients treated with tivozanib. The NRP-1 will be evaluated as a biomarker for tivozanib response in future clinical trials. Ongoing clinical trial will further characterize activity of tivozanib in hepatocellular carcinoma, sarcomas, and gynecologic cancers.
authors.affiliation: Division of Hematology and Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, 1720 2nd Avenue South, NP2540N, Birmingham, AL, 35294, USA.
authors.forename: Muhammad Omer
authors.initials: MO
authors.lastname: Jamil
authors.forename: Amanda
authors.initials: A
authors.lastname: Hathaway
authors.forename: Amitkumar
authors.initials: A
authors.lastname: Mehta
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy*; D010671:Phenylurea Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011804:Quinolines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C553176:tivozanib; D040262:Receptors, Vascular Endothelial Growth Factor