Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial

被引：230

作者：

Motzer, Robert J. ^{[1
]}

Escudier, Bernard ^{[2
]}

George, Saby ^{[3
]}

Hammers, Hans J. ^{[4
]}

Srinivas, Sandhya ^{[5
]}

Tykodi, Scott S. ^{[6
,7
]}

Sosman, Jeffrey A. ^{[8
]}

Plimack, Elizabeth R. ^{[9
]}

Procopio, Giuseppe ^{[10
]}

McDermott, David F. ^{[11
]}

Castellano, Daniel ^{[12
]}

Choueiri, Toni K. ^{[13
]}

Donskov, Frede ^{[14
]}

Gurney, Howard ^{[15
,16
]}

Oudard, Stephane ^{[17
]}

Richardet, Martin ^{[18
]}

Peltola, Katriina ^{[19
]}

Alva, Ajjai S. ^{[20
]}

Carducci, Michael ^{[21
]}

Wagstaff, John ^{[22
,23
]}

Chevreau, Christine ^{[24
]}

Fukasawa, Satoshi ^{[25
,26
]}

Tomita, Yoshihiko ^{[27
]}

Gauler, Thomas C. ^{[28
]}

Kollmannsberger, Christian K. ^{[29
]}

Schutz, Fabio A. ^{[30
]}

Larkin, James ^{[31
]}

Cella, David ^{[32
]}

McHenry, M. Brent ^{[33
]}

Saggi, Shruti Shally ^{[34
]}

Tannir, Nizar M. ^{[35
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[2] Gustave Roussy, Dept Med Oncol, Villejuif, France

[3] Roswell Park Canc Inst, Dept Med, Buffalo, NY 14263 USA

[4] UT Southwestern Kidney Canc Program, Div Hematol & Oncol, Dallas, TX USA

[5] Stanford Univ, Med Ctr, Stanford Canc Inst, Stanford, CA 94305 USA

[6] Univ Washington, Dept Med, Seattle, WA USA

[7] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA

[8] Northwestern Univ, Med Ctr, Dept Hematol Oncol, Chicago, IL 60611 USA

[9] Fox Chase Canc Ctr, Dept Hematol Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA

[10] Fdn Ist Nazl Tumori, Milan, Italy

[11] Beth Israel Deaconess Med Ctr, Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA

[12] Hosp Univ 12 Octubre, Oncol Med, Madrid, Spain

[13] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA

[14] Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark

[15] Westmead Hosp, Dept Med Oncol, Westmead, NSW, Australia

[16] Macquarie Univ, Westmead, NSW, Australia

[17] Hop Europeen Georges Pompidou, AP HP, Serv Cancerol Med, Paris, France

[18] Inst Oncol Cordoba, Fdn Richardet Longo, Cordoba, Argentina

[19] Helsinki Univ Hosp, Comprehens Canc Ctr, Helsinki, Finland

[20] Univ Michigan, Div Hematol & Oncol, Ann Arbor, MI 48109 USA

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

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

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

[24] Inst Univ Canc Toulouse Oncopole, Inst Claudius Regaud, Toulouse, France

[25] Chiba Canc Ctr, Prostate Ctr, Chiba, Japan

[26] Chiba Canc Ctr, Div Urol, Chiba, Japan

[27] Niigata Univ, Dept Urol, Dept Mol Oncol, Grad Sch Med & Dent Sci, Niigata, Japan

[28] Univ Duisburg Essen, Univ Hosp Essen, Dept Med, Duisburg, Germany

[29] BC Canc Vancouver Canc Ctr, Div Med Oncol, Vancouver, BC, Canada

[30] Beneficencia Portuguesa Sao Paulo, Sao Paulo, Brazil

[31] Royal Marsden Hosp NHS Fdn Trust, London, England

[32] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA

[33] Bristol Myers Squibb, Dept Biostat, Princeton, NJ USA

[34] Bristol Myers Squibb, Dept Clin Trials, Princeton, NJ USA

[35] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

来源：

CANCER | 2020年 / 126卷 / 18期

关键词：

advanced renal cell carcinoma (aRCC); CheckMate; 025; everolimus; immune checkpoint inhibitor; nivolumab; previously treated; DOSE RECOMBINANT INTERLEUKIN-2; SURVIVAL; SAFETY; LIFE;

D O I：

10.1002/cncr.33033

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background CheckMate 025 has shown superior efficacy for nivolumab over everolimus in patients with advanced renal cell carcinoma (aRCC) along with improved safety and tolerability. This analysis assesses the long-term clinical benefits of nivolumab versus everolimus. Methods The randomized, open-label, phase 3 CheckMate 025 trial (NCT01668784) included patients with clear cell aRCC previously treated with 1 or 2 antiangiogenic regimens. Patients were randomized to nivolumab (3 mg/kg every 2 weeks) or everolimus (10 mg once a day) until progression or unacceptable toxicity. The primary endpoint was overall survival (OS). The secondary endpoints were the confirmed objective response rate (ORR), progression-free survival (PFS), safety, and health-related quality of life (HRQOL). Results Eight hundred twenty-one patients were randomized to nivolumab (n = 410) or everolimus (n = 411); 803 patients were treated (406 with nivolumab and 397 with everolimus). With a minimum follow-up of 64 months (median, 72 months), nivolumab maintained an OS benefit in comparison with everolimus (median, 25.8 months [95% CI, 22.2-29.8 months] vs 19.7 months [95% CI, 17.6-22.1 months]; hazard ratio [HR], 0.73; 95% CI, 0.62-0.85) with 5-year OS probabilities of 26% and 18%, respectively. ORR was higher with nivolumab (94 of 410 [23%] vs 17 of 411 [4%];P < .001). PFS also favored nivolumab (HR, 0.84; 95% CI, 0.72-0.99;P = .0331). The most common treatment-related adverse events of any grade were fatigue (34.7%) and pruritus (15.5%) with nivolumab and fatigue (34.5%) and stomatitis (29.5%) with everolimus. HRQOL improved from baseline with nivolumab but remained the same or deteriorated with everolimus. Conclusions The superior efficacy of nivolumab over everolimus is maintained after extended follow-up with no new safety signals, and this supports the long-term benefits of nivolumab monotherapy in patients with previously treated aRCC. LAY SUMMARY CheckMate 025 compared the effects of nivolumab (a novel immunotherapy) with those of everolimus (an older standard-of-care therapy) for the treatment of advanced kidney cancer in patients who had progressed on antiangiogenic therapy. After 5 years of study, nivolumab continues to be better than everolimus in extending the lives of patients, providing a long-lasting response to treatment, and improving quality of life with a manageable safety profile. The results demonstrate that the clinical benefits of nivolumab versus everolimus in previously treated patients with advanced kidney cancer continue in the long term.

引用

页码：4156 / 4167

页数：12

共 25 条

[11]

COX DR, 1972, J R STAT SOC B, V34, P187

[12]

Fisher RI, 2000, CANCER J SCI AM, V6, pS55

[13] RESULTS OF TREATMENT OF 255 PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA WHO RECEIVED HIGH-DOSE RECOMBINANT INTERLEUKIN-2 THERAPY [J].

FYFE, G ;

FISHER, RI ;

ROSENBERG, SA ;

SZNOL, M ;

PARKINSON, DR ;

LOUIE, AC .

JOURNAL OF CLINICAL ONCOLOGY, 1995, 13 (03) :688-696

[14] Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade [J].

Iwai, Y ;

Ishida, M ;

Tanaka, Y ;

Okazaki, T ;

Honjo, T ;

Minato, N .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (19) :12293-12297

[15] NONPARAMETRIC-ESTIMATION FROM INCOMPLETE OBSERVATIONS [J].

KAPLAN, EL ;

MEIER, P .

JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1958, 53 (282) :457-481

[16] Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab [J].

McDermott, David F. ;

Drake, Charles G. ;

Sznol, Mario ;

Choueiri, Toni K. ;

Powderly, John D. ;

Smith, David C. ;

Brahmer, Julie R. ;

Carvajal, Richard D. ;

Hammers, Hans J. ;

Puzanov, Igor ;

Hodi, F. Stephen ;

Kluger, Harriet M. ;

Topalian, Suzanne L. ;

Pardoll, Drew M. ;

Wigginton, Jon M. ;

Kollia, Georgia D. ;

Gupta, Ashok ;

McDonald, Dan ;

Sankar, Vindira ;

Sosman, Jeffrey A. ;

Atkins, Michael B. .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (18) :2013-U42

[17]

McFarlane J, 2017, 16 INT KIDN CANC S N

[18] Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma [J].

Motzer, R. J. ;

Escudier, B. ;

McDermott, D. F. ;

George, S. ;

Hammers, H. J. ;

Srinivas, S. ;

Tykodi, S. S. ;

Sosman, J. A. ;

Procopio, G. ;

Plimack, E. R. ;

Castellano, D. ;

Choueiri, T. K. ;

Gurney, H. ;

Donskov, F. ;

Bono, P. ;

Wagstaff, J. ;

Gauler, T. C. ;

Ueda, T. ;

Tomita, Y. ;

Schutz, F. A. ;

Kollmannsberger, C. ;

Larkin, J. ;

Ravaud, A. ;

Simon, J. S. ;

Xu, L-A ;

Waxman, I. M. ;

Sharma, P. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (19) :1803-1813

[19] Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial [J].

Motzer, Robert ;

Rini, Brian, I ;

McDermott, David F. ;

Frontera, Osvaldo Aren ;

Hammers, Hans J. ;

Carducci, Michael A. ;

Salman, Pamela ;

Escudier, Bernard ;

Beuselinck, Benoit ;

Amin, Asim ;

Porta, Camillo ;

George, Saby ;

Neiman, Victoria ;

Bracarda, Sergio ;

Tykodi, Scott S. ;

Barthelemy, Philippe ;

Leibowitz-Amit, Raya ;

Plimack, Elizabeth R. ;

Oosting, Sjoukje F. ;

Redman, Bruce ;

Melichar, Bohusiav ;

Powles, Thomas ;

Nathan, Paul ;

Oudard, Stephan ;

Pook, David ;

Choueiri, Toni K. ;

Donskov, Frede ;

Grimm, Marc-Oliver ;

Gurney, Howard ;

Heng, Daniel Y. C. ;

Kollmannsberger, Christian K. ;

Harrison, Michael R. ;

Tamita, Yoshihiko ;

Duran, Ignacio ;

Gruenwold, Viktor ;

McHenry, M. Brent ;

Mekan, Sabeen ;

Tannir, Nizar M. .

LANCET ONCOLOGY, 2019, 20 (10) :1370-1385

[20] Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial [J].

Motzer, Robert J. ;

Rini, Brian I. ;

McDermott, David F. ;

Redman, Bruce G. ;

Kuzel, Timothy M. ;

Harrison, Michael R. ;

Vaishampayan, Ulka N. ;

Drabkin, Harry A. ;

George, Saby ;

Logan, Theodore F. ;

Margolin, Kim A. ;

Plimack, Elizabeth R. ;

Lambert, Alexandre M. ;

Waxman, Ian M. ;

Hammers, Hans J. .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (13) :1430-1437

← 1 2 3 →