Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma

R. J. Motzer, N. M. Tannir, D. F. McDermott, O. Arén Frontera, B. Melichar, T. K. Choueiri, E. R. Plimack, P. Barthélémy, C. Porta, S. George, T. Powles, F. Donskov, V. Neiman, C. K. Kollmannsberger, P. Salman, H. Gurney, R. Hawkins, A. Ravaud, M. O. Grimm, S. Bracarda & 12 others C. H. Barrios, Y. Tomita, D. Castellano, B. I. Rini, A. C. Chen, S. Mekan, M. B. McHenry, M. Wind-Rotolo, J. Doan, P. Sharma, H. J. Hammers, B. Escudier

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Abstract

BACKGROUND: Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. METHODS: We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk. RESULTS: A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month overall survival rate was 75% (95% confidence interval [CI], 70 to 78) with nivolumab plus ipilimumab and 60% (95% CI, 55 to 65) with sunitinib; the median overall survival was not reached with nivolumab plus ipilimumab versus 26.0 months with sunitinib (hazard ratio for death, 0.63; P<0.001). The objective response rate was 42% versus 27% (P<0.001), and the complete response rate was 9% versus 1%. The median progression-free survival was 11.6 months and 8.4 months, respectively (hazard ratio for disease progression or death, 0.82; P = 0.03, not significant per the prespecified 0.009 threshold). Treatment-related adverse events occurred in 509 of 547 patients (93%) in the nivolumab-plus-ipilimumab group and 521 of 535 patients (97%) in the sunitinib group; grade 3 or 4 events occurred in 250 patients (46%) and 335 patients (63%), respectively. Treatment-related adverse events leading to discontinuation occurred in 22% and 12% of the patients in the respective groups. CONCLUSIONS: Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma.

Original languageEnglish (US)
Pages (from-to)1277-1290
Number of pages14
JournalNew England Journal of Medicine
Volume378
Issue number14
DOIs
StatePublished - Apr 5 2018

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Renal Cell Carcinoma
Disease-Free Survival
Survival
ipilimumab
sunitinib
nivolumab
Confidence Intervals
Disease Progression
Survival Rate
Body Weight

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Motzer, R. J., Tannir, N. M., McDermott, D. F., Arén Frontera, O., Melichar, B., Choueiri, T. K., ... Escudier, B. (2018). Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. New England Journal of Medicine, 378(14), 1277-1290. https://doi.org/10.1056/NEJMoa1712126

Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. / Motzer, R. J.; Tannir, N. M.; McDermott, D. F.; Arén Frontera, O.; Melichar, B.; Choueiri, T. K.; Plimack, E. R.; Barthélémy, P.; Porta, C.; George, S.; Powles, T.; Donskov, F.; Neiman, V.; Kollmannsberger, C. K.; Salman, P.; Gurney, H.; Hawkins, R.; Ravaud, A.; Grimm, M. O.; Bracarda, S.; Barrios, C. H.; Tomita, Y.; Castellano, D.; Rini, B. I.; Chen, A. C.; Mekan, S.; McHenry, M. B.; Wind-Rotolo, M.; Doan, J.; Sharma, P.; Hammers, H. J.; Escudier, B.

In: New England Journal of Medicine, Vol. 378, No. 14, 05.04.2018, p. 1277-1290.

Research output: Contribution to journalArticle

Motzer, RJ, Tannir, NM, McDermott, DF, Arén Frontera, O, Melichar, B, Choueiri, TK, Plimack, ER, Barthélémy, P, Porta, C, George, S, Powles, T, Donskov, F, Neiman, V, Kollmannsberger, CK, Salman, P, Gurney, H, Hawkins, R, Ravaud, A, Grimm, MO, Bracarda, S, Barrios, CH, Tomita, Y, Castellano, D, Rini, BI, Chen, AC, Mekan, S, McHenry, MB, Wind-Rotolo, M, Doan, J, Sharma, P, Hammers, HJ & Escudier, B 2018, 'Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma', New England Journal of Medicine, vol. 378, no. 14, pp. 1277-1290. https://doi.org/10.1056/NEJMoa1712126
Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK et al. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. New England Journal of Medicine. 2018 Apr 5;378(14):1277-1290. https://doi.org/10.1056/NEJMoa1712126
Motzer, R. J. ; Tannir, N. M. ; McDermott, D. F. ; Arén Frontera, O. ; Melichar, B. ; Choueiri, T. K. ; Plimack, E. R. ; Barthélémy, P. ; Porta, C. ; George, S. ; Powles, T. ; Donskov, F. ; Neiman, V. ; Kollmannsberger, C. K. ; Salman, P. ; Gurney, H. ; Hawkins, R. ; Ravaud, A. ; Grimm, M. O. ; Bracarda, S. ; Barrios, C. H. ; Tomita, Y. ; Castellano, D. ; Rini, B. I. ; Chen, A. C. ; Mekan, S. ; McHenry, M. B. ; Wind-Rotolo, M. ; Doan, J. ; Sharma, P. ; Hammers, H. J. ; Escudier, B. / Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. In: New England Journal of Medicine. 2018 ; Vol. 378, No. 14. pp. 1277-1290.
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abstract = "BACKGROUND: Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. METHODS: We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk. RESULTS: A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month overall survival rate was 75{\%} (95{\%} confidence interval [CI], 70 to 78) with nivolumab plus ipilimumab and 60{\%} (95{\%} CI, 55 to 65) with sunitinib; the median overall survival was not reached with nivolumab plus ipilimumab versus 26.0 months with sunitinib (hazard ratio for death, 0.63; P<0.001). The objective response rate was 42{\%} versus 27{\%} (P<0.001), and the complete response rate was 9{\%} versus 1{\%}. The median progression-free survival was 11.6 months and 8.4 months, respectively (hazard ratio for disease progression or death, 0.82; P = 0.03, not significant per the prespecified 0.009 threshold). Treatment-related adverse events occurred in 509 of 547 patients (93{\%}) in the nivolumab-plus-ipilimumab group and 521 of 535 patients (97{\%}) in the sunitinib group; grade 3 or 4 events occurred in 250 patients (46{\%}) and 335 patients (63{\%}), respectively. Treatment-related adverse events leading to discontinuation occurred in 22{\%} and 12{\%} of the patients in the respective groups. CONCLUSIONS: Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma.",
author = "Motzer, {R. J.} and Tannir, {N. M.} and McDermott, {D. F.} and {Ar{\'e}n Frontera}, O. and B. Melichar and Choueiri, {T. K.} and Plimack, {E. R.} and P. Barth{\'e}l{\'e}my and C. Porta and S. George and T. Powles and F. Donskov and V. Neiman and Kollmannsberger, {C. K.} and P. Salman and H. Gurney and R. Hawkins and A. Ravaud and Grimm, {M. O.} and S. Bracarda and Barrios, {C. H.} and Y. Tomita and D. Castellano and Rini, {B. I.} and Chen, {A. C.} and S. Mekan and McHenry, {M. B.} and M. Wind-Rotolo and J. Doan and P. Sharma and Hammers, {H. J.} and B. Escudier",
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language = "English (US)",
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TY - JOUR

T1 - Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma

AU - Motzer, R. J.

AU - Tannir, N. M.

AU - McDermott, D. F.

AU - Arén Frontera, O.

AU - Melichar, B.

AU - Choueiri, T. K.

AU - Plimack, E. R.

AU - Barthélémy, P.

AU - Porta, C.

AU - George, S.

AU - Powles, T.

AU - Donskov, F.

AU - Neiman, V.

AU - Kollmannsberger, C. K.

AU - Salman, P.

AU - Gurney, H.

AU - Hawkins, R.

AU - Ravaud, A.

AU - Grimm, M. O.

AU - Bracarda, S.

AU - Barrios, C. H.

AU - Tomita, Y.

AU - Castellano, D.

AU - Rini, B. I.

AU - Chen, A. C.

AU - Mekan, S.

AU - McHenry, M. B.

AU - Wind-Rotolo, M.

AU - Doan, J.

AU - Sharma, P.

AU - Hammers, H. J.

AU - Escudier, B.

PY - 2018/4/5

Y1 - 2018/4/5

N2 - BACKGROUND: Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. METHODS: We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk. RESULTS: A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month overall survival rate was 75% (95% confidence interval [CI], 70 to 78) with nivolumab plus ipilimumab and 60% (95% CI, 55 to 65) with sunitinib; the median overall survival was not reached with nivolumab plus ipilimumab versus 26.0 months with sunitinib (hazard ratio for death, 0.63; P<0.001). The objective response rate was 42% versus 27% (P<0.001), and the complete response rate was 9% versus 1%. The median progression-free survival was 11.6 months and 8.4 months, respectively (hazard ratio for disease progression or death, 0.82; P = 0.03, not significant per the prespecified 0.009 threshold). Treatment-related adverse events occurred in 509 of 547 patients (93%) in the nivolumab-plus-ipilimumab group and 521 of 535 patients (97%) in the sunitinib group; grade 3 or 4 events occurred in 250 patients (46%) and 335 patients (63%), respectively. Treatment-related adverse events leading to discontinuation occurred in 22% and 12% of the patients in the respective groups. CONCLUSIONS: Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma.

AB - BACKGROUND: Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. METHODS: We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk. RESULTS: A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month overall survival rate was 75% (95% confidence interval [CI], 70 to 78) with nivolumab plus ipilimumab and 60% (95% CI, 55 to 65) with sunitinib; the median overall survival was not reached with nivolumab plus ipilimumab versus 26.0 months with sunitinib (hazard ratio for death, 0.63; P<0.001). The objective response rate was 42% versus 27% (P<0.001), and the complete response rate was 9% versus 1%. The median progression-free survival was 11.6 months and 8.4 months, respectively (hazard ratio for disease progression or death, 0.82; P = 0.03, not significant per the prespecified 0.009 threshold). Treatment-related adverse events occurred in 509 of 547 patients (93%) in the nivolumab-plus-ipilimumab group and 521 of 535 patients (97%) in the sunitinib group; grade 3 or 4 events occurred in 250 patients (46%) and 335 patients (63%), respectively. Treatment-related adverse events leading to discontinuation occurred in 22% and 12% of the patients in the respective groups. CONCLUSIONS: Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma.

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