A randomized, phase 3 EORTC trial involving patients with resected, high-risk stage III melanoma – published this week in NEJM and presented at the first Presidential Symposium at ESMO – demonstrated that adjuvant treatment with the checkpoint inhibitor ipilimumab significantly improves overall survival, distant metastasis-free survival and recurrence- free survival compared with placebo.
At a 5.3 year median follow-up, Ipilimumab treatment improved the five-year rates by approximately 10% for all efficacy end points: overall survival (65.4% vs 54.4%), distant metastasis-free survival (48.3% vs 38.9%) and recurrence-free survival (40.8% vs 30.3%). The risk of death was reduced by 28% with ipilimumab compared with placebo, and the risk of distant metastasis or death, as well the risk of recurrence or death were reduced by 24%.
“Few options are available for high-risk Stage 3 melanoma patients, only half of whom usually remain disease-free four years post-surgery,” said Dr Alexander Eggermont, author of the NEJM publication and Principal investigator for the study. “These results show patients would now have a compelling adjuvant treatment option that can make a significant difference on their overall survival, with manageable toxicity levels.”
While patients treated with ipilimumab demonstrated increased risk of immune-related adverse events, most commonly gastrointestinal (16.1%), hepatic (10.8%) and endocrine (7.9%), these events were successfully managed in the majority of patients with established treatment guidelines.
“This is another example of how EORTC, through its network and with its solid base of expertise, can conduct large, complex trials in innovative fields such as immunotherapy with high-quality results,” said Denis Lacombe, EORTC Director General. “Our infrastructure offers the perfect setting for pivotal studies that can bring significant improvements to cancer patients’ lives with practice-changing independent clinical trials.”
The EORTC 18071 study, which was conducted in partnership with Bristol-Myers Squibb, included 951 adult patients with cutaneous melanoma metastatic to regional lymph nodes who had undergone complete resection within 12 weeks before randomization. In the trial, which involved 99 centers across 19 countries, patients were randomly assigned to receive either an intravenous infusion of ipilimumab 10 mg/kg or placebo for up to 3 years. Ipilumab is a human monoclonal antibody blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) to augment antitumor immune responses.
This research underscores the long history of large clinical trials conducted by EORTC in the field of melanoma, notably in the adjuvant setting, which have contributed to establish new standards of care.