The most common grade 3–4 immune-related adverse events in the ipilimumab group were gastrointestinal (75 [16%] vs 4 [<1%] in the placebo group), hepatic (50 [11%] vs 1 [<1%]), and endocrine (40 [8%] vs 0). Toxicity led to discontinuation of treatment in more than half the patients in the ipilimumab group, and less than a third of patients received a year of ipilimumab treatment.
According to a commentary, use of recurrence-free survival as the primary endpoint is of concern as overall survival has been the primary endpoint of almost all previous melanoma adjuvant trials, and many oncologists have insisted on seeing a significant overall survival benefit before recommending potentially toxic adjuvant treatment to a patient who is disease-free after surgery. The commentators suggest that while overall survival data and pending data from a trial directly comparing adjuvant ipilimumab with interferon are awaited, use of adjuvant ipilimumab must be assessed solely on its effect on recurrence-free survival versus placebo. They consider that at present, these results establish checkpoint inhibitors can favourably affect the natural history of minimal residual disease.