Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.
Choueiri, Toni K. M.D.; Escudier, Bernard M.D.; Powles, Thomas M.D.; Mainwaring, Paul N. M.D.; Rini, Brian I. M.D.; Donskov, Frede M.D., Ph.D.; Hammers, Hans M.D., Ph.D.; Hutson, Thomas E. D.O., Pharm.D.; Lee, Jae-Lyun M.D., Ph.D.; Peltola, Katriina M.D., Ph.D.; Roth, Bruce J. M.D.; Bjarnason, Georg A. M.D.; Geczi, Lajos M.D., Ph.D.; Keam, Bhumsuk M.D., Ph.D.; Maroto, Pablo M.D.; Heng, Daniel Y.C. M.D., M.P.H; Schmidinger, Manuela M.D.; Kantoff, Philip W. M.D.; Borgman-Hagey, Anne M.D.; Hessel, Colin M.S.; Scheffold, Christian M.D., Ph.D.; Schwab, Gisela M. M.D.; Tannir, Nizar M. M.D.; Motzer, Robert J. M.D.; the METEOR Investigators *
[Article]
New England Journal of Medicine.
373(19):1814-1823, November 5, 2015.
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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. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.)
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