Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

被引：4878

作者：

Motzer, R. J. ^{[1
]}

Escudier, B. ^{[3
]}

McDermott, D. F. ^{[5
]}

George, S. ^{[2
]}

Hammers, H. J. ^{[8
]}

Srinivas, S. ^{[9
]}

Tykodi, S. S. ^{[10
,11
]}

Sosman, J. A. ^{[12
]}

Procopio, G. ^{[13
]}

Plimack, E. R. ^{[14
]}

Castellano, D. ^{[15
]}

Choueiri, T. K. ^{[6
,7
]}

Gurney, H. ^{[16
,17
]}

Donskov, F. ^{[18
]}

Bono, P. ^{[19
,20
]}

Wagstaff, J. ^{[21
,22
]}

Gauler, T. C. ^{[24
]}

Ueda, T. ^{[25
]}

Tomita, Y. ^{[26
]}

Schutz, F. A. ^{[27
]}

Kollmannsberger, C. ^{[28
]}

Larkin, J. ^{[23
]}

Ravaud, A. ^{[4
]}

Simon, J. S. ^{[29
]}

Xu, L-A ^{[30
]}

Waxman, I. M. ^{[29
]}

Sharma, P. ^{[31
]}

机构：

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

[2] Roswell Pk Canc Inst, Buffalo, NY 14263 USA

[3] Inst Gustave Roussy, Villejuif, France

[4] Hop St Andre, Bordeaux Univ Hosp, Bordeaux, France

[5] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[6] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Boston, MA USA

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

[9] Stanford Canc Inst, Stanford, CA USA

[10] Univ Washington, Seattle, WA 98195 USA

[11] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[12] Vanderbilt Univ, Med Ctr, Nashville, TN USA

[13] Fdn Ist Nazl Tumori, Milan, Italy

[14] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA

[15] Hosp Univ 12 Octubre, Madrid, Spain

[16] Westmead Hosp, Sydney, NSW, Australia

[17] Macquarie Univ, Sydney, NSW 2109, Australia

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

[19] Helsinki Univ Cent Hosp, Helsinki, Finland

[20] Univ Helsinki, Helsinki, Finland

[21] South West Wales Canc Inst, Swansea, W Glam, Wales

[22] Swansea Univ, Coll Med, Swansea, W Glam, Wales

[23] Royal Marsden Hosp, London SW3 6JJ, England

[24] Univ Duisburg Essen, Univ Hosp Essen, Duisburg, Germany

[25] Chiba Canc Ctr, Chiba 2608717, Japan

[26] Niigata Univ, Niigata, Japan

[27] Hosp Sao Jose, Beneficencia Portuguesa Sao Paulo, Sao Paulo, Brazil

[28] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada

[29] Bristol Myers Squibb Co, Lawrenceville, NJ USA

[30] Bristol Myers Squibb Co, Hopewell, NJ USA

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

来源：

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

关键词：

ANTI-PROGRAMMED DEATH-1; PROGNOSTIC-FACTORS; SURVIVAL; CONFIDENCE; SAFETY; B7-H1;

D O I：

10.1056/NEJMoa1510665

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. METHODS A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1: 1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. RESULTS The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P <= 0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%). CONCLUSIONS Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus.

引用

页码：1803 / 1813

页数：11

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