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  3. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial

Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial

  • J Clin Oncol. 2013 Oct 20;31(30):3791-9. doi: 10.1200/JCO.2012.47.4940.
Robert J Motzer 1,  Dmitry Nosov,  Timothy Eisen,  Igor Bondarenko,  Vladimir Lesovoy,  Oleg Lipatov,  Piotr Tomczak,  Oleksiy Lyulko,  Anna Alyasova,  Mihai Harza,  Mikhail Kogan,  Boris Y Alekseev,  Cora N Sternberg,  Cezary Szczylik,  David Cella,  Cristina Ivanescu,  Andrew Krivoshik,  Andrew Strahs,  Brooke Esteves,  Anna Berkenblit,  Thomas E Hutson
Affiliations

Affiliation

  • 1 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.
PMID: 24019545 DOI: 10.1200/JCO.2012.47.4940
Abstract

Purpose: Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1/Flt-1), -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.

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