An improvement in overall survival among patients with metastatic melanoma has been
an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated
antigen 4 to potentiate an antitumor T-cell response--administered with or without
a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients
with previously treated metastatic melanoma.
A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma,
whose disease had progressed while they were receiving therapy for metastatic disease,
were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients),
ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram
of body weight, was administered with or without gp100 every 3 weeks for up to four
treatments (induction). Eligible patients could receive reinduction therapy. The primary
end point was overall survival.
The median overall survival was 10.0 months among patients receiving ipilimumab plus
gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio
for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1
months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003).
No difference in overall survival was detected between the ipilimumab groups (hazard
ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse
events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated
with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were
associated with immune-related adverse events.
Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone,
improved overall survival in patients with previously treated metastatic melanoma.
Adverse events can be severe, long-lasting, or both, but most are reversible with
appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov
number, NCT00094653.)