Ipilimumab (Yervoy®) is a fully human monoclonal immunoglobulin (Ig) G1 antibody that can block the interaction between B7 and CTLA-4 proteins and consequently activates a cytotoxic T-lymphocyte-mediated immune response against cancer cells. Recently, ipilimumab was approved for the adjuvant treatment of patients with high-risk stage III melanoma by the Food and Drug Administration (FDA) in the U.S.

This report is based on the analysis of the EORTC 18071 trial, a randomised double-blind phase III trial, which was conducted to assess the efficacy of adjuvant therapy with ipilimumab on all survival endpoints of patients with high-risk stage III cutaneous melanoma after complete regional lymph node dissection. Between 10 July 2008 and 1 August 2011, a total of 951 patients were randomly assigned to receive either ipilimumab (n=475) or placebo (n=476). The stratification of randomisation was based on disease stages and geographic regions. On 31st January 2016 (cut-off date), 506 events of distant metastases or death and 376 deaths had occurred. At a median follow-up of 5.3 years, the primary endpoint; recurrence-free survival rate at five years (+10.5%), as well as the secondary endpoints; overall survival rate (+11.0%) and rate of distant metastasis-free survival at five years (+9.4%) were significantly improved in the ipilimumab group compared to the placebo group. However, no data on median OS and median progression-free survival were available at the time of data cut-off. In terms of safety, there was a 40.0% difference in grade ≥3 immune-related adverse events in the ipilimumab group, and five patients (1.1%) died due to immune-related adverse events, before the start of the maintenance therapy. In total, 240 of 471 patients (51.0%) discontinued treatment due to an ipilimumab-induced adverse event. Moreover, no clinically relevant differences in global health status scores were observed during or after induction therapy between the two treatment groups. Overall, even though the administration of ipilimumab increases the rate of toxicities, no statistically significant differences in health-related quality of life scores between the treatment groups have been observed.

Nevertheless, the identification of predictive biomarkers may be crucial in order to further improve response rates and outcomes, and to reduce severe adverse events. In addition, ongoing studies remain to be seen in order to gain comparable results. Finally, aiming for a reduction of immune therapy costs (annual ipilimumab therapy costs: € 435,850.10) may be a crucial step in the near future.