Entry Detail
| General information | |
| Database: | DB00483 |
| Objective: | Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), 2, and 3. Thisphase III trial compared tivozanib with sorafenib as initial targeted therapy in patients with metastatic renal cell carcinoma (RCC). |
| Authors: | Motzer RJ, et al |
| Title: | Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 24019545 |
| Trial Design | |
| Clinical Trial Id: | NCT01030783 |
| Agent: | tivozanib |
| Target: | VEGF2 receptor Vascular endothelial growth factor receptor 3 Vascular endothelial growth factor receptor 1 |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | renal cell carcinoma with a clear cell component |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | openlabel, randomizedphase III trial |
| Key Patients Feature: | Eligibility criteria included written informed consent; age 18 years;priornephrectomy;histologicallyconfirmedRCCwithaclearcellcomponentand recurrence or metastases; measurable disease per Response EvaluationCriteria in Solid Tumors (RECIST) criteria; Eastern Cooperative OncologyGroup performance status (ECOG PS) 0 to 1; and adequate hematologic, renal, and hepatic function. Patients could be treatmentnaive or could havereceivedoneorfetheyrpriorsystemictreatments(immunotherapy, chemotherapy, orhormonaltherapy)formetastaticRCC.Priorsystemictherapygivenasan adjuvant following nephrectomy was counted as a prior therapy if recurrence was detected within 6 months of completing treatment. Prior VEGFtargeted therapies or mammalian target of rapamycin-targeted therapy werenot permitted. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Tivozanib versus sorafenib |
| Treatment Info: | Tivozanib was administeredorally at 1.5mg once per day every day for 3 weeks follotheyd by 1 week off (onecycle is 3 weeks on, 1 week off). Sorafenib was administered orally at a dose of 400mg(two 200mg tablets)twice per day continuously(one cycle is 4 weekson). |
| Primary End Point: | progression free survival (PFS) |
| Secondary End Point: | NA |
| Patients Number: | 517 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | The confirmed ORR for tivozanib, based on blinded independent radiology review of tumor response, was 33.1% (95% CI, 27.4% to 39.2%) versus 23.3% (95% CI, 18.3% to 29.0%) for sorafenib (Table 2; P = .014). The ORR for tivozanib, based on investigator assessment, was 35.4% (95% CI, 29.6% to 41.5%) versus 30.7% (95% CI, 25.2% to 36.8%) for sorafenib (P = .260). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 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). |
| Median OS A vs. C: | 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=0.105). |
| Adverse Event(agent arm): | 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 handfoot skin reaction (54% v 14%) and diarrhea (33% v 23%). |
| Conclusions: | Tivozanib demonstrated improved PFS, but not OS, and a differentiated safety profile, compared with sorafenib, as initial targeted therapy for metastatic RCC. |