Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma Academic Article uri icon

abstract

  • BACKGROUND:Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS:We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. RESULTS:At a minimum follow-up of 36 months, the median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group. CONCLUSIONS:Among patients with advanced melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505 .).

authors

  • Wolchok, Jedd D
  • Chiarion-Sileni, Vanna
  • Gonzalez, Rene
  • Rutkowski, Piotr
  • Grob, Jean-Jacques
  • Cowey, C Lance
  • Lao, Christopher D
  • Wagstaff, John
  • Schadendorf, Dirk
  • Ferrucci, Pier F
  • Smylie, Michael
  • Dummer, Reinhard
  • Hill, Andrew
  • Hogg, David
  • Haanen, John
  • Carlino, Matteo S
  • Bechter, Oliver
  • Maio, Michele
  • Marquez-Rodas, Ivan
  • Guidoboni, Massimo
  • McArthur, Grant
  • LebbĂ©, Celeste
  • Ascierto, Paolo A
  • Long, Georgina V
  • Cebon, Jonathan
  • Sosman, Jeffrey
  • Postow, Michael A
  • Callahan, Margaret K
  • Walker, Dana
  • Rollin, Linda
  • Bhore, Rafia
  • Hodi, F Stephen
  • Larkin, James

publication date

  • 2017