Melanoma survival extension with adjuvant ipilimumab comes at toxicity cost
medwireNews: Updated phase III trial results show that ipilimumab treatment improves overall survival (OS) and distant metastasis-free survival in stage III melanoma patients who have undergone complete resection, but with increased toxicity relative to placebo.
These findings – simultaneously presented at the ESMO 2016 Congress, held in Copenhagen, Denmark, and published in The New England Journal of Medicine – follow on from the primary analysis, which showed significantly longer recurrence-free survival with ipilimumab than placebo, said the presenting author.
In the EORTC 18071 trial, 475 stage III melanoma patients with a high recurrence risk were randomly allocated to receive adjuvant ipilimumab 10 mg/kg every 3 weeks for four doses, after which the drug was given every 12 weeks for a maximum of 3 years. Their 476 counterparts received placebo according to the same schedule.
At 5 years, 65.4% of ipilimumab-treated patients were alive, compared with 54.4% of those given placebo, equating to a significant hazard ratio (HR) of 0.72.
The rate of distant metastasis-free survival at 5 years was also significantly higher in the ipilimumab than the placebo group, at 48.3% versus 38.9%, with an HR for death or distant metastasis of 0.76.
This clinical benefit comes at a price though, said presenter Alexander Eggermont (Gustave Roussy Cancer Campus Grand Paris and University Paris–Sud, Villejuif, France), with almost double the proportion of patients in the ipilimumab than placebo treatment arm experiencing a grade 3 or 4 side effect (54.1 vs 26.2%).
Immune-related adverse events were also more common in patients who received ipilimumab relative to those given placebo, with grade 3 or 4 episodes occurring in 41.6% and 2.7% of participants, respectively. The most frequent categories were gastrointestinal (16.1%), hepatic (10.8%) and endocrine (7.9%).
The study authors report that the majority of grade 2, 3 or 4 immune-related toxicities resolved within a median of 4–8 weeks with the use of established management guidelines, but endocrinopathies took longer, at a median resolution time of 54 weeks.
There were five deaths attributable to side effects related to ipilimumab treatment – three from colitis and one each from myocarditis and multi-organ failure associated with Guillain–Barré syndrome.
Speaking at the conference, Eggermont stressed that the drug can only be given “in centers that have experience with ipilimumab and where patients are meticulously instructed, in case of onset of diarrhea and other symptoms, to get in touch with their ipilimumab prescribing physician.”
“Otherwise, safety is not guaranteed,” he added, emphasizing the need for education.
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