Ipilimumab improves survival in previously treated, advanced melanoma patients with poor prognosis factors: Subgroup analyses from a phase III trial.

Background: Ipilimumab is a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor T-cell response. In a phase III, randomized controlled trial (MDX010-20), ipilimumab improved overall survival (OS) in patients with previously treated, advanced melanoma (O’Day et al. ASCO 2010, Abstr 02). We conducted a subgroup analysis of OS for patients in this trial with poor prognostic factors, e.g., M1c disease with/without elevated serum lactate dehydrogenase (LDH). Methods: 676 HLA-A*0201-positive patients with previously treated, unresectable stage III or IV melanoma were randomized 3:1:1 to ipilimumab plus a gp100 melanoma peptide vaccine (n=403), ipilimumab alone (n=137), or gp100 alone (n=136). Ipilimumab at 3 mg/kg and/or gp100 were administered every 3 weeks for up to four treatments (induction). Patients with a history of CNS metastases who had undergone prior treatment were allowed. The Kaplan-Meier method was used to estimate OS, Cox proportional-hazards models to estimate hazard ratios, and log-rank test for p-values. Results: Ipilimumab, alone or in combination with gp100 peptide vaccine, improved OS compared with gp100 alone (Table). Across treatment groups, more than 70% of patients had M1c disease and more than 36% had elevated LDH levels at baseline. In these subgroups, ipilimumab showed a statistically significant improvement in OS compared with gp100 alone (Table). A total of 77 patients with a history of brain metastases received treatment (42 in the combination group, 15 in the ipilimumabalone group, and 20 in the gp100-alone group). Ongoing analyses include OS for the subgroup of patients with a history of brain metastases. Conclusions: Ipilimumab improves OS in previously treated, advanced melanoma patients with good and poor prognostic factors. Survival analyses of patients with brain metastases will also be presented.