| General information |
| Database: | DB00465 |
| Objective: | This randomized, openlabel, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renalcell carcinoma that had progressed after VEGFRtargeted therapy. |
| Authors: | Choueiri TK, et al |
| Title: | Cabozantinib versus Everolimus in Advanced RenalCell Carcinoma. |
| Journal: | N Engl J Med |
| Year: | 2015 |
| PMID: | 26406150 |
| Trial Design |
| Clinical Trial Id: | NCT01865747 |
| Agent: | cabozantinib
|
| Target: | Hepatocyte growth factor receptor, Vascular endothelial growth factor receptor 2
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | randomized, phase III trial |
| Key Patients Feature: | Eligible patients were 18 years of age or olderwith advanced or metastatic renalcell carcinomawith a clearcell component and measurabledisease. Patients must have received prior treatment with at least one VEGFRtargeting tyrosinekinase inhibitor and must have had radiographicprogression during treatment or within 6 monthsafter the most recent dose of the VEGFR inhibitor. Patients with known brain metastases thatwere adequately treated and stable were eligible.There was no limit to the number of previousanticancer therapies, which could include cytokines, chemotherapy, and monoclonal antibodies, including those targeting VEGF, the programmed death 1 (PD1) receptor, or its ligandPDL1. Eligible patients also had a Karnofskyperformancestatus score of at least 70% (on ascale from 0 to 100%, with higher scores indicating better performance status) and adequateorgan and marrow function. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Cabozantinib versus Everolimus |
| Treatment Info: | They randomly assigned patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. |
| Primary End Point: | PFS |
| Secondary End Point: | overall survival and objective response rate. |
| Patients Number: | 658 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.4 months with cabozantinib and 3.8 months with everolimus. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus |
| Conclusions: | progression free survival was longer with cabozantinib than with everolimus among patients with renalcell carcinoma that had progressed after VEGFRtargeted therapy. |