In Europe, ipilimumab is currently licensed only for pre-treated patients. However, one phase III trial compared ipilimumab + dacarbazine to placebo + dacarbazine in previously untreated patients. In this trial, overall survival was significantly longer in the ipilimumab group, but the gain was with 2.1 months rather modest. Moreover, although the duration of response was considerably longer in the combination arm than in the control arm, responses occurred in both groups only in a minority of patients and were not statistically significant between the two groups. In terms of adverse events (AEs), the incidence of grade 3 or grade 4 AEs, foremost driven by immune-related AEs, was also higher in the combination arm than in the dacarbazine + placebo group. Subsequently, considerably more patients stopped treatment due to drug-related AEs in the ipilimumab + dacarbazine group.
Open questions associated with first-line ipilimumab therapy concern, for example, which dosing regimen should be used, a factor considerably influencing costs. Identifying both further selection criteria and other agents ipilimumab can be combined with, may yield better results.