Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma
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Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. / Choueiri, Toni K; Escudier, Bernard; Powles, Thomas; Mainwaring, Paul N; Rini, Brian I; Donskov, Frede; Hammers, Hans; Hutson, Thomas E; Lee, Jae-Lyun; Peltola, Katriina; Roth, Bruce J; Bjarnason, Georg A; Géczi, Lajos; Keam, Bhumsuk; Maroto, Pablo; Heng, Daniel Y C; Schmidinger, Manuela; Kantoff, Philip W; Borgman-Hagey, Anne; Hessel, Colin; Scheffold, Christian; Schwab, Gisela M; Tannir, Nizar M; Motzer, Robert J; METEOR Investigators.
In: NEW ENGL J MED, Vol. 373, No. 19, 05.11.2015, p. 1814-23.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma
AU - Choueiri, Toni K
AU - Escudier, Bernard
AU - Powles, Thomas
AU - Mainwaring, Paul N
AU - Rini, Brian I
AU - Donskov, Frede
AU - Hammers, Hans
AU - Hutson, Thomas E
AU - Lee, Jae-Lyun
AU - Peltola, Katriina
AU - Roth, Bruce J
AU - Bjarnason, Georg A
AU - Géczi, Lajos
AU - Keam, Bhumsuk
AU - Maroto, Pablo
AU - Heng, Daniel Y C
AU - Schmidinger, Manuela
AU - Kantoff, Philip W
AU - Borgman-Hagey, Anne
AU - Hessel, Colin
AU - Scheffold, Christian
AU - Schwab, Gisela M
AU - Tannir, Nizar M
AU - Motzer, Robert J
AU - METEOR Investigators
PY - 2015/11/5
Y1 - 2015/11/5
N2 - 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.).
AB - 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.).
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Anilides
KW - Antineoplastic Agents
KW - Carcinoma, Renal Cell
KW - Disease-Free Survival
KW - Female
KW - Humans
KW - Kidney Neoplasms
KW - Male
KW - Middle Aged
KW - Pyridines
KW - Quality of Life
KW - Sirolimus
KW - Survival Analysis
U2 - 10.1056/NEJMoa1510016
DO - 10.1056/NEJMoa1510016
M3 - SCORING: Journal article
C2 - 26406150
VL - 373
SP - 1814
EP - 1823
JO - NEW ENGL J MED
JF - NEW ENGL J MED
SN - 0028-4793
IS - 19
ER -