PURPOSE: 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).
PATIENTS AND 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%).
CONCLUSION: Tivozanib demonstrated improved PFS, but not OS, and a differentiated safety profile, compared with sorafenib, as initial targeted therapy for metastatic RCC.
Motzer RJ, Nosov D, Eisen T, Bondarenko I, Lesovoy V, Lipatov O, Tomczak P, Lyulko O, Alyasova A, Harza M, Kogan M, Alekseev BY, Sternberg CN, Szczylik C, Cella D, Ivanescu C, Krivoshik A, Strahs A, Esteves B, Berkenblit A, Hutson TE. Are you the author?
Memorial Sloan-Kettering Cancer Center, New York, NY; N.N. Blokhin Cancer Research Center; Federal State Institution, Moscow Research Oncological Institute, Moscow; State Budget Medical Institution, Republican Clinical Oncological Center, Bashkortostan; Federal Budget Medical Institution, Privolzhsky District Medical Center, Nizhny Novgorod; State Budget Higher Educational Institute, The Rostov State Medical University, Rostov-on-Don, Russia; Cambridge University Health Partners, Cambridge, United Kingdom; Dnipropetrovsk State Medical Academy under the Ministry of Health of Ukraine, Dnipropetrovsk; V.I. Shapoval Regional Clinical Center for Urology and Nephrology, Kharkiv; Zaporizhia Medical Academy of Postgraduate Education, Zaporizhia, Ukraine; Clinical Hospital No. 1 of the Poznan University of Medical Sciences, Poznań; Military Institute of Health, Warsaw, Poland; Fundeni Clinical Institute, Bucharest, Romania; San Camillo and Forlanini Hospitals, Rome, Italy; Northwestern University Feinberg School of Medicine, Chicago; Astellas Pharma Global Development, Northbrook, IL; Quintiles, Hoofddorp, The Netherlands; AVEO Oncology, Cambridge, MA; Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX.
Reference: J Clin Oncol. 2013 Oct 20;31(30):3791-9.