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Clinical Trial
. 2013 Oct 20;31(30):3791-9.
doi: 10.1200/JCO.2012.47.4940. Epub 2013 Sep 9.

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

Robert J Motzer  1 , 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
Affiliations
Clinical Trial

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

Robert J Motzer et al. J Clin Oncol. .

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 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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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram based on data cutoff date of December 15, 2011. AE, adverse event; PFS, progression-free survival. (*) Includes patient deaths that occurred on study drug any time after first dose but before patient being discontinued from study drug for any reason.
Fig 2.
Fig 2.
Kaplan-Meier plot of progression-free survival (PFS) as determined by independent radiology review. (A) Overall intent-to-treat population; (B) no prior treatment.
Fig 3.
Fig 3.
Forest plot: subgroup hazard ratios for progression-free survival and their 95% CIs. ECOG status, Eastern Cooperative Oncology Group performance score; MSKCC, Memorial Sloan-Kettering Cancer Center.
Fig 4.
Fig 4.
Overall survival of the intent-to-treat population.
Fig A1.
Fig A1.
Kaplan-Meier plot of progression-free survival (PFS) as determined by investigator assessment in intent-to-treat population.
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