title: Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial.
abstract: OBJECTIVE
  Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), -2, and -3. This phase III trial compared tivozanib with sorafenib as initial targeted therapy in patients with metastatic renal cell carcinoma (RCC).
  
  
  METHODS
  Patients with metastatic RCC, with a clear cell component, prior nephrectomy, measurable disease, and 0 or 1 prior therapies for metastatic RCC were randomly assigned to tivozanib or sorafenib. Prior VEGF-targeted therapy and mammalian target of rapamycin inhibitor were not permitted. The primary end point was progression-free survival (PFS) by independent review.
  
  
  RESULTS
  A total of 517 patients were randomly assigned to tivozanib (n = 260) or sorafenib (n = 257). PFS was longer with tivozanib than with sorafenib in the overall population (median, 11.9 v 9.1 months; hazard ratio [HR], 0.797; 95% CI, 0.639 to 0.993; P = .042). One hundred fifty-six patients (61%) who progressed on sorafenib crossed over to receive tivozanib. The final overall survival (OS) analysis showed a trend toward longer survival on the sorafenib arm than on the tivozanib arm (median, 29.3 v 28.8 months; HR, 1.245; 95% CI, 0.954 to 1.624; P = .105). Adverse events (AEs) more common with tivozanib than with sorafenib were hypertension (44% v 34%) and dysphonia (21% v 5%). AEs more common with sorafenib than with tivozanib were hand-foot skin reaction (54% v 14%) and diarrhea (33% v 23%).
  
  
  CONCLUSIONS
  Tivozanib demonstrated improved PFS, but not OS, and a differentiated safety profile, compared with sorafenib, as initial targeted therapy for metastatic RCC.
authors.affiliation: Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York, NY; Dmitry Nosov, N.N. Blokhin Cancer Research Center; Boris Y. Alekseev, Federal State Institution, Moscow Research Oncological Institute, Moscow; Oleg Lipatov, State Budget Medical Institution, Republican Clinical Oncological Center, Bashkortostan; Anna Alyasova, Federal Budget Medical Institution, Privolzhsky District Medical Center, Nizhny Novgorod; Mikhail Kogan, State Budget Higher Educational Institute, The Rostov State Medical University, Rostov-on-Don, Russia; Timothy Eisen, Cambridge University Health Partners, Cambridge, United Kingdom; Igor Bondarenko, Dnipropetrovsk State Medical Academy under the Ministry of Health of Ukraine, Dnipropetrovsk; Vladimir Lesovoy, V.I. Shapoval Regional Clinical Center for Urology and Nephrology, Kharkiv; Oleksiy Lyulko, Zaporizhia Medical Academy of Postgraduate Education, Zaporizhia, Ukraine; Piotr Tomczak, Clinical Hospital No. 1 of the Poznan University of Medical Sciences, Poznań; Cezary Szczylik, Military Institute of Health, Warsaw, Poland; Mihai Harza, Fundeni Clinical Institute, Bucharest, Romania; Cora N. Sternberg, San Camillo and Forlanini Hospitals, Rome, Italy; David Cella, Northwestern University Feinberg School of Medicine, Chicago; Andrew Krivoshik, Astellas Pharma Global Development, Northbrook, IL; Cristina Ivanescu, Quintiles, Hoofddorp, the Netherlands; Brooke Esteves, Anna Berkenblit, Andrew Strahs, AVEO Oncology, Cambridge, MA; Thomas E. Hutson, Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: Dmitry
authors.initials: D
authors.lastname: Nosov
authors.forename: Timothy
authors.initials: T
authors.lastname: Eisen
authors.forename: Igor
authors.initials: I
authors.lastname: Bondarenko
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lesovoy
authors.forename: Oleg
authors.initials: O
authors.lastname: Lipatov
authors.forename: Piotr
authors.initials: P
authors.lastname: Tomczak
authors.forename: Oleksiy
authors.initials: O
authors.lastname: Lyulko
authors.forename: Anna
authors.initials: A
authors.lastname: Alyasova
authors.forename: Mihai
authors.initials: M
authors.lastname: Harza
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kogan
authors.forename: Boris Y
authors.initials: BY
authors.lastname: Alekseev
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: Cezary
authors.initials: C
authors.lastname: Szczylik
authors.forename: David
authors.initials: D
authors.lastname: Cella
authors.forename: Cristina
authors.initials: C
authors.lastname: Ivanescu
authors.forename: Andrew
authors.initials: A
authors.lastname: Krivoshik
authors.forename: Andrew
authors.initials: A
authors.lastname: Strahs
authors.forename: Brooke
authors.initials: B
authors.lastname: Esteves
authors.forename: Anna
authors.initials: A
authors.lastname: Berkenblit
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006304:Health Status; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D009392:Nephrectomy; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016017:Odds Ratio; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011788:Quality of Life; D011804:Quinolines / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011804:Quinolines; C553176:tivozanib; D009536:Niacinamide; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor
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