Tivozanib versus sorafenib as initial targeted therapy for patients with
metastatic renal cell carcinoma: results from a phase III trial.
Author(s): Motzer RJ(1), 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.
Affiliation(s): Author information:
(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, PoznaĆ;
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.
Publication date & source: 2013, J Clin Oncol. , 31(30):3791-9
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.
|