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

Authors

Robert J. Motzer, Memorial Sloan-Kettering Cancer Center
Dmitry Nosov, Cancer Research Center
Timothy Eisen, Cambridge University Health Partners
Igor Bondarenko, State Establishment Dnipropetrovsk Medical Academy of Health Ministry of Ukraine
Vladimir Lesovoy, 'Regional Medical Clinical Center of Urology and Nephrology n.a. V.I. Shapoval'
Oleg Lipatov, Republican Clinical Oncological Dispensary
Piotr Tomczak, Poznan University of Medical Sciences
Oleksiy Lyulko, Zaporizhzhya Medical Academy of Postgraduate Education
Anna Alyasova, Privolzhsky Research Medical University
Mihai Harza, Institutul Clinic Fundeni
Mikhail Kogan, Rostov State Medical University
Boris Y. Alekseev, P. A. Gerzen Institute of Oncology
Cora N. Sternberg, Azienda Ospedaliera San Camillo Forlanini
Cezary Szczylik, Wojskowy Instytut Medyczny
David Cella, Northwestern University Feinberg School of Medicine
Cristina Ivanescu, IQVIA Inc.
Andrew Krivoshik, Astellas Pharma US, Inc.
Andrew Strahs, AVEO Oncology
Brooke Esteves, AVEO Oncology
Anna Berkenblit, AVEO Oncology
Thomas E. Hutson, Baylor Charles A. Sammons Cancer Center

Document Type

Journal Article

Publication Date

10-20-2013

Journal

Journal of Clinical Oncology

Volume

31

Issue

30

DOI

10.1200/JCO.2012.47.4940

Abstract

© 2013 by American Society of Clinical Oncology. 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.

APA Citation

Motzer, R., Nosov, D., Eisen, T., Bondarenko, I., Lesovoy, V., Lipatov, O., Tomczak, P., Lyulko, O., Alyasova, A., Harza, M., Kogan, M., Alekseev, B., Sternberg, C., Szczylik, C., Cella, D., Ivanescu, C., Krivoshik, A., Strahs, A., Esteves, B., Berkenblit, A., & Hutson, T. (2013). Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: Results from a phase III trial. Journal of Clinical Oncology, 31 (30). http://dx.doi.org/10.1200/JCO.2012.47.4940