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 & 8 others Christian Kollmannsberger, James Larkin, Alain Ravaud, Jason S. Simon, Li An Xu, Ian M. Waxman, Padmanee Sharma, CheckMate 025 Investigators

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages1803-1813
Number of pages11
JournalNew England Journal of Medicine
Volume373
Issue number19
DOIs
Publication statusPublished - 5 Nov 2015

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Renal Cell Carcinoma
Confidence Intervals
Survival
Everolimus
nivolumab
Therapeutics
Tablets
Disease-Free Survival
Fatigue
Anemia
Odds Ratio
Body Weight
Safety

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Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., ... CheckMate 025 Investigators (2015). Nivolumab versus everolimus in advanced renal-cell carcinoma. New England Journal of Medicine, 373(19), 1803-1813. https://doi.org/10.1056/NEJMoa1510665
Motzer, Robert J. ; Escudier, Bernard ; McDermott, David F. ; George, Saby ; Hammers, Hans J. ; Srinivas, Sandhya ; Tykodi, Scott S. ; Sosman, Jeffrey A. ; Procopio, Giuseppe ; Plimack, Elizabeth R. ; Castellano, Daniel ; Choueiri, Toni K. ; Gurney, Howard ; Donskov, Frede ; Bono, Petri ; Wagstaff, John ; Gauler, Thomas C. ; Ueda, Takeshi ; Tomita, Yoshihiko ; Schutz, Fabio A. ; Kollmannsberger, Christian ; Larkin, James ; Ravaud, Alain ; Simon, Jason S. ; Xu, Li An ; Waxman, Ian M. ; Sharma, Padmanee ; CheckMate 025 Investigators. / Nivolumab versus everolimus in advanced renal-cell carcinoma. In: New England Journal of Medicine. 2015 ; Vol. 373, No. 19. pp. 1803-1813.
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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.",
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 Xu, {Li An} and Waxman, {Ian M.} and Padmanee Sharma and {CheckMate 025 Investigators}",
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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, LA, Waxman, IM, Sharma, P & CheckMate 025 Investigators 2015, 'Nivolumab versus everolimus in advanced renal-cell carcinoma', New England Journal of Medicine, vol. 373, no. 19, pp. 1803-1813. https://doi.org/10.1056/NEJMoa1510665

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

In: New England Journal of Medicine, Vol. 373, No. 19, 05.11.2015, p. 1803-1813.

Research output: Contribution to journalArticleResearchpeer-review

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

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.

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.

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DO - 10.1056/NEJMoa1510665

M3 - Article

VL - 373

SP - 1803

EP - 1813

JO - New England Journal of Medicine

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JF - New England Journal of Medicine

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Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. New England Journal of Medicine. 2015 Nov 5;373(19):1803-1813. https://doi.org/10.1056/NEJMoa1510665