Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

被引：976

作者：

Choueiri, T. K. ^{[1
]}

Escudier, B. ^{[2
]}

Powles, T. ^{[3
]}

Mainwaring, P. N. ^{[4
]}

Rini, B. I. ^{[5
]}

Donskov, F. ^{[6
]}

Hammers, H. ^{[7
]}

Hutson, T. E. ^{[8
]}

Lee, J-L ^{[9
]}

Peltola, K. ^{[11
]}

Roth, B. J. ^{[12
]}

Bjarnason, G. A. ^{[13
]}

Geczi, L. ^{[15
]}

Keam, B. ^{[10
]}

Maroto, P. ^{[16
]}

Heng, D. Y. C. ^{[14
]}

Schmidinger, M. ^{[17
]}

Kantoff, P. W. ^{[1
]}

Borgman-Hagey, A. ^{[18
]}

Hessel, C. ^{[18
]}

Scheffold, C. ^{[18
]}

Schwab, G. M. ^{[18
]}

Tannir, N. M. ^{[19
]}

Motzer, R. J. ^{[20
]}

机构：

[1] Dana Farber Canc Inst, Boston, MA 02215 USA

[2] Inst Gustave Roussy, Villejuif, France

[3] Queen Mary Univ London, Royal Free NHS Trust, Canc Res UK Expt Canc Med Ctr, Barts Canc Inst, London, England

[4] Icon Canc Care, South Brisbane, Qld, Australia

[5] Cleveland Clin, Cleveland, OH USA

[6] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark

[7] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA

[8] Baylor Univ, Charles A Sammons Canc Ctr, Texas Oncol, Dallas, TX USA

[9] Univ Ulsan, Coll Med, Seoul, South Korea

[10] Seoul Natl Univ Hosp, Seoul 110744, South Korea

[11] Univ Helsinki, Cent Hosp, Ctr Canc, Helsinki, Finland

[12] Washington Univ, St Louis, MO 63130 USA

[13] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada

[14] Tom Baker Canc Clin, Calgary, AB, Canada

[15] Natl Inst Oncol, Budapest, Hungary

[16] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[17] Med Univ Vienna, Vienna, Austria

[18] Exelixis, San Francisco, CA USA

[19] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[20] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2015年 / 373卷 / 19期

关键词：

PHASE-III TRIAL; PROGNOSTIC-FACTORS; HGF/C-MET; C-MET; SUNITINIB; TUMORS; METASTASIS; XL184; NEPHRECTOMY; SORAFENIB;

D O I：

10.1056/NEJMoa1510016

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1814 / 1823

页数：10

共 29 条

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