Cabozantinib versus everolimus in advanced renal-cell carcinoma

Toni K. Choueiri, Bernard Escudier, Thomas Powles, Paul N. Mainwaring, Brian I. Rini, Frede Donskov, Hans Hammers, Thomas E. Hutson, Jae Lyun Lee, Katriina Peltola, Bruce J. Roth, Georg A. Bjarnason, Lajos Geczi, Bhumsuk Keam, Pablo Maroto, Daniel Y.C. Heng, Manuela Schmidinger, Philip W. Kantoff, Anne Borgman-Hagey, Colin HesselChristian Scheffold, Gisela M. Schwab, Nizar M. Tannir, Robert J. Motzer

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Abstract

BACKGROUND Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. METHODS We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression- free survival. Secondary efficacy end points were overall survival and objective response rate. RESULTS Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005) but did not cross the significance boundary for the interim analysis. 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 renal-cell carcinoma that had progressed after VEGFR-targeted therapy.

Original languageEnglish
Pages (from-to)1814-1823
Number of pages10
JournalNew England Journal of Medicine
Volume373
Issue number19
DOIs
Publication statusPublished - Nov 5 2015

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ASJC Scopus subject areas

  • Medicine(all)

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Choueiri, T. K., Escudier, B., Powles, T., Mainwaring, P. N., Rini, B. I., Donskov, F., Hammers, H., Hutson, T. E., Lee, J. L., Peltola, K., Roth, B. J., Bjarnason, G. A., Geczi, L., Keam, B., Maroto, P., Heng, D. Y. C., Schmidinger, M., Kantoff, P. W., Borgman-Hagey, A., ... Motzer, R. J. (2015). Cabozantinib versus everolimus in advanced renal-cell carcinoma. New England Journal of Medicine, 373(19), 1814-1823. https://doi.org/10.1056/NEJMoa1510016