Τρίτη 30 Μαΐου 2017

Efficacy and safety of sequential use of everolimus in Japanese patients with advanced renal cell carcinoma after failure of first-line treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitor: a multicenter phase II clinical trial

Abstract
Objective
Many studies have shown the efficacy of everolimus after pretreatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated the efficacy and safety of everolimus as a second-line treatment after the failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy in Japanese patients with advanced renal cell carcinoma.
Methods
This was an open-label, multicenter, phase II trial conducted in Japan through the central registration system. A total of 57  patients were enrolled. Patients were administered 10 mg of everolimus q.d. orally. The primary efficacy endpoint was progression-free survival achieved by administration of everolimus.
Results
The median progression-free survival of patients administered everolimus was 5.03 months (95% confidence interval: 3.70–6.20). The median overall survival was not reached. The objective response rate was 9.4% (95% confidence interval: 3.1–20.7). The progression-free survival in the group of <100% relative dose intensity was 6.70 months (95% confidence interval: 4.13–11.60), and that in the group of 100% relative dose intensity was 3.77 months (hazard ratio: 2.79, 95% confidence interval: 2.77–5.63). The commonly observed adverse events and laboratory abnormalities were stomatitis (49.1%), hypertriglyceridemia (26.4%), interstitial lung disease (26.4%), anemia (22.6%) and hypercholesterolemia (22.6%).
Conclusion
The median progression-free survival was almost similar to that recorded in the RECORD-1 study, whereas prolongation of overall survival was observed in the present study compared with the RECORD-1 study. The treatment outcomes of first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy and second-line everolimus treatment in Japanese patients were successfully established in the present study.

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