{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T18:07:48Z","timestamp":1792951668787,"version":"4.5.0"},"reference-count":40,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"30","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2013,10,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> 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). <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> 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%). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Tivozanib demonstrated improved PFS, but not OS, and a differentiated safety profile, compared with sorafenib, as initial targeted therapy for metastatic RCC. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2012.47.4940","type":"journal-article","created":{"date-parts":[[2013,9,10]],"date-time":"2013-09-10T02:31:19Z","timestamp":1378780279000},"page":"3791-3799","source":"Crossref","is-referenced-by-count":350,"title":["Tivozanib Versus Sorafenib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma: Results From a Phase III Trial"],"prefix":"10.1200","volume":"31","author":[{"given":"Robert J.","family":"Motzer","sequence":"first","affiliation":[{"name":"Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York, NY; Dmitry Nosov, N.N. 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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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Lesovoy","sequence":"additional","affiliation":[{"name":"Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York, NY; Dmitry Nosov, N.N. Blokhin Cancer Research Center; Boris Y. 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