Robert J Motzer1, 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. 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.
Abstract
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 receivetivozanib. 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.
RCT Entities:
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.
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