Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial Journal Article
| Authors: | Motzer, R. J.; Nosov, D.; Eisen, T.; Bondarenko, I.; Lesovoy, V.; Lipatov, O.; Tomczak, P.; Lyulko, O.; Alyasova, A.; Harza, M.; Kogan, M.; Alekseev, B. Y.; Sternberg, C. N.; Szczylik, C.; Cella, D.; Ivanescu, C.; Krivoshik, A.; Strahs, A.; Esteves, B.; Berkenblit, A.; Hutson, T. E. |
| Article Title: | Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial |
| Abstract: | 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 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. 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%). Tivozanib demonstrated improved PFS, but not OS, and a differentiated safety profile, compared with sorafenib, as initial targeted therapy for metastatic RCC. |
| Keywords: | adult; controlled study; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; sorafenib; antineoplastic agents; receptors, vascular endothelial growth factor; adjuvant therapy; comparative study; disease free survival; neoadjuvant therapy; cancer staging; methodology; antineoplastic agent; neoplasm staging; vasculotropin receptor; quality of life; controlled clinical trial; randomized controlled trial; odds ratio; pathology; kidney carcinoma; kidney neoplasms; nephrectomy; risk; drug antagonism; health status; kidney tumor; carcinoma, renal cell; drug derivative; phase 3 clinical trial; kaplan meier method; molecularly targeted therapy; nicotinamide; kaplan-meier estimate; quinolines; quinoline derivative; molecular targeted therapy; niacinamide; tivozanib; phenylurea compounds; very elderly; carbanilamide derivative; humans; human; male; female; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 31 |
| Issue: | 30 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2013-10-20 |
| Start Page: | 3791 |
| End Page: | 3799 |
| Language: | English |
| PUBMED: | 24019545 |
| PROVIDER: | scopus |
| DOI: | 10.1200/jco.2012.47.4940 |
| PMCID: | PMC5569677 |
| DOI/URL: | |
| Notes: | Cited By (since 1996):1 -- Export Date: 3 February 2014 -- Source: Scopus |
