Research in context
Evidence before this study
To identify other studies of ipilimumab in melanoma, we searched PubMed and congress abstracts from the annual meetings of the American Society of Clinical Oncology, the European Society for Medical Oncology, and the Society for Melanoma Research for articles published in English between Jan 1, 2010, and July 31, 2016. Our search terms included “ipilimumab”, “anti-CTLA-4”, “BMS-734016”, “MDX-010”, and “MDX-101”. We focused on survival results in melanoma. Ipilimumab was the first drug to show a survival improvement in patients with metastatic melanoma in a randomised controlled phase 3 trial. Together, efficacy data across phase 2 and phase 3 studies show an overall survival benefit for both 3 mg/kg and 10 mg/kg doses of ipilimumab compared with controls. Additional data from a dose-ranging phase 2 study suggest longer survival with the 10 mg/kg dose than with lower doses. No studies done so far permit conclusive comparison of ipilimumab 10 mg/kg with ipilimumab 3 mg/kg.
Added value of this study
When the two doses of ipilimumab were directly compared in this study, overall survival was significantly improved with the 10 mg/kg dose compared with the 3 mg/kg dose, whereas the 3 mg/kg dose had a more favourable safety profile and a survival benefit consistent with that seen in other ipilimumab 3 mg/kg studies in advanced melanoma. Quality of life generally worsened during the ipilimumab induction phase treatment, and this worsening seemed to be more pronounced with 10 mg/kg compared with 3 mg/kg. However, insufficient duration of follow-up prevents conclusions to be drawn regarding the long-term effect of ipilimumab on quality of life.
Implications of all the available evidence
The treatment landscape for first-line treatment of patients with advanced melanoma has changed since this study was initiated, with ipilimumab being succeeded by newer treatments. However, the increased survival benefit of ipilimumab 10 mg/kg compared with 3 mg/kg suggests that the clinical utility of ipilimumab in refractory patients with high unmet medical need could warrant further assessment.