Patient Preference for Tivozanib Hydrochloride or Sunitinib in the Treatment of Metastatic Renal Cell Carcinoma (MRCC): Taurus Study

ABSTRACT Purpose Tivozanib hydrochloride is a potent, selective, long half-life inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Inhibition of VEGF-driven angiogenesis is known to reduce vascularization and tumor growth. Currently, sunitinib is most commonly used as first-line treatment in patients with mRCC. Previous Phase II and Phase III studies have demonstrated the promising efficacy and safety of tivozanib in patients with mRCC. The primary objective of this study is to compare patient preferences for tivozanib or sunitinib. Secondary objectives include assessing overall safety and tolerability, frequency of dose modifications, and quality of life in patients treated with tivozanib and sunitinib.Study design: This Phase II, randomized, double-blind, multinational, crossover study will compare the preference of mRCC patients for tivozanib or sunitinib as treatment for metastatic disease. Recruitment of 160 patients is planned. Patients will be randomized to tivozanib 1.5 mg/d for 12 weeks (wks) (Cycle = 3 wks on, 1 wk off) or sunitinib 50 mg/d for 12 wks (Cycle = 4 wks on, 2 wks off). After a washout period, patients will cross over to the alternate treatment (sunitinib or tivozanib). Methods After 12 wks of treatment, tumor response will be assessed using Response Evaluation Criteria In Solid Tumors (version 1.1). Patients are expected to cross over to the second treatment for 12 wks; however patients with a significant clinical response (defined as >50% tumor reduction or complete response for non-measurable disease) will be given the option to continue the first treatment if they choose. Patients with Grade 3/4 adverse events may have a dose interruption of ≤2 wks to manage toxicities, after which they may continue at the same or reduced dose; dose reductions to 1.0 mg/d for tivozanib and 37.5 mg/d for sunitinib will be allowed. After the second 12-wk period, patients' drug preferences, based on a questionnaire, and their tumor response will be assessed and reviewed prior to a final tumor assessment. Conclusion The double-blind design of this study will enable comprehensive assessment of patient preference for tivozanib and sunitinib as treatment for mRCC. Disclosure B. Escudier: Board Membership:Pfizer, GSK, Bayer, AVEO, Novartis Consultancy: Pfizer, GSK, Bayer, Payment for lectures, service on spkrs bureaus:Pfizer, Novartis Payment for development of educational presentations: Pfizer, GSK, Bayer, AVEO, Novartis. L. Steelman: Current Employment: AVEO with stock options Employment: Novartis until 8/11 Employment: ARIAD until 11/09. D. Cesic: AVEO Pharmaceuticals employee with stock options. A. Berkenblit: AVEO Pharmaceuticals employee with stock options