Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

Robert J Motzer; Bernard Escudier; David F McDermott; Saby George; Hans J Hammers; Sandhya Srinivas; Scott S Tykodi; Jeffrey A Sosman; Giuseppe Procopio; Elizabeth R Plimack; Daniel Castellano; Toni K Choueiri; Howard Gurney; Frede Donskov; Petri Bono; John Wagstaff; Thomas C Gauler; Takeshi Ueda; Yoshihiko Tomita; Fabio A Schutz; Christian Kollmannsberger; James Larkin; Alain Ravaud; Jason S Simon; Li-An Xu; Ian M Waxman; Padmanee Sharma; CheckMate 025 Investigators (Poul Geertsen, members)

doi:10.1056/NEJMoa1510665

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

Robert J Motzer, Bernard Escudier, David F McDermott, Saby George, Hans J Hammers, Sandhya Srinivas, Scott S Tykodi, Jeffrey A Sosman, Giuseppe Procopio, Elizabeth R Plimack, Daniel Castellano, Toni K Choueiri, Howard Gurney, Frede Donskov, Petri Bono, John Wagstaff, Thomas C Gauler, Takeshi Ueda, Yoshihiko Tomita, Fabio A SchutzChristian Kollmannsberger, James Larkin, Alain Ravaud, Jason S Simon, Li-An Xu, Ian M Waxman, Padmanee Sharma, CheckMate 025 Investigators (Poul Geertsen, members)

Kræftbehandling

4818 Citationer (Scopus)

Abstract

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. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).

Originalsprog	Engelsk
Tidsskrift	The New England journal of medicine
Vol/bind	373
Udgave nummer	19
Sider (fra-til)	1803-13
Antal sider	11
ISSN	0028-4793
DOI	https://doi.org/10.1056/NEJMoa1510665
Status	Udgivet - 5 nov. 2015

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10.1056/NEJMoa1510665

Citationsformater

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., ... CheckMate 025 Investigators (Poul Geertsen, members) (2015). Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. The New England journal of medicine, 373(19), 1803-13. https://doi.org/10.1056/NEJMoa1510665

Motzer, RJ, Escudier, B, McDermott, DF, George, S, Hammers, HJ, Srinivas, S, Tykodi, SS, Sosman, JA, Procopio, G, Plimack, ER, Castellano, D, Choueiri, TK, Gurney, H, Donskov, F, Bono, P, Wagstaff, J, Gauler, TC, Ueda, T, Tomita, Y, Schutz, FA, Kollmannsberger, C, Larkin, J, Ravaud, A, Simon, JS, Xu, L-A, Waxman, IM, Sharma, P & CheckMate 025 Investigators (Poul Geertsen, members) 2015, 'Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma', The New England journal of medicine, bind 373, nr. 19, s. 1803-13. https://doi.org/10.1056/NEJMoa1510665

@article{7a59d9ee8c9b4e97bb7e920bb97842c9,

title = "Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma",

abstract = "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. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Carcinoma, Renal Cell, Everolimus, Female, Humans, Kidney Neoplasms, Male, Middle Aged, Quality of Life, Sirolimus, Survival Analysis, Young Adult",

author = "Motzer, {Robert J} and Bernard Escudier and McDermott, {David F} and Saby George and Hammers, {Hans J} and Sandhya Srinivas and Tykodi, {Scott S} and Sosman, {Jeffrey A} and Giuseppe Procopio and Plimack, {Elizabeth R} and Daniel Castellano and Choueiri, {Toni K} and Howard Gurney and Frede Donskov and Petri Bono and John Wagstaff and Gauler, {Thomas C} and Takeshi Ueda and Yoshihiko Tomita and Schutz, {Fabio A} and Christian Kollmannsberger and James Larkin and Alain Ravaud and Simon, {Jason S} and Li-An Xu and Waxman, {Ian M} and Padmanee Sharma and {CheckMate 025 Investigators (Poul Geertsen, members)} and Geertsen, {Poul F.}",

year = "2015",

month = nov,

day = "5",

doi = "10.1056/NEJMoa1510665",

language = "English",

volume = "373",

pages = "1803--13",

journal = "The New England journal of medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "19",

}

TY - JOUR

T1 - Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

AU - Motzer, Robert J

AU - Escudier, Bernard

AU - McDermott, David F

AU - George, Saby

AU - Hammers, Hans J

AU - Srinivas, Sandhya

AU - Tykodi, Scott S

AU - Sosman, Jeffrey A

AU - Procopio, Giuseppe

AU - Plimack, Elizabeth R

AU - Castellano, Daniel

AU - Choueiri, Toni K

AU - Gurney, Howard

AU - Donskov, Frede

AU - Bono, Petri

AU - Wagstaff, John

AU - Gauler, Thomas C

AU - Ueda, Takeshi

AU - Tomita, Yoshihiko

AU - Schutz, Fabio A

AU - Kollmannsberger, Christian

AU - Larkin, James

AU - Ravaud, Alain

AU - Simon, Jason S

AU - Xu, Li-An

AU - Waxman, Ian M

AU - Sharma, Padmanee

AU - CheckMate 025 Investigators (Poul Geertsen, members)

A2 - Geertsen, Poul F.

PY - 2015/11/5

Y1 - 2015/11/5

N2 - 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. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).

AB - 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. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Monoclonal

KW - Antineoplastic Agents

KW - Carcinoma, Renal Cell

KW - Everolimus

KW - Female

KW - Humans

KW - Kidney Neoplasms

KW - Male

KW - Middle Aged

KW - Quality of Life

KW - Sirolimus

KW - Survival Analysis

KW - Young Adult

U2 - 10.1056/NEJMoa1510665

DO - 10.1056/NEJMoa1510665

M3 - Journal article

C2 - 26406148

SN - 0028-4793

VL - 373

SP - 1803

EP - 1813

JO - The New England journal of medicine

JF - The New England journal of medicine

IS - 19

ER -

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

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