Adjuvant ipilimumab may significantly improve recurrence-free survival for patients with completely resected, high-risk stage III melanoma, according to a new randomized, double-blind phase III study published in The Lancet Oncology.
Adjuvant ipilimumab may significantly improve recurrence-free survival for patients with completely resected, high-risk stage III melanoma, according to a new randomized, double-blind phase III study published in The Lancet Oncology. Researchers found that the adverse event profile was consistent with that observed in advanced melanoma. However, they found that endocrinopathies were significantly higher.
Professor Alexander Eggermont, MD, who is with Gustave Roussy Cancer Campus Grand Paris, Villejuif, France, and colleagues compared adjuvant ipilimumab to placebo in patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) with adequate resection of lymph nodes. None of the patients had received previous systemic therapy for melanoma and the patients were enrolled at 91 hospitals located in 19 countries.
For this study, the patients were randomly assigned to receive intravenous infusions of 10 mg/kg ipilimumab or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. The investigators randomized and stratified patients based on disease stage and geographical region. The primary endpoint of this study was recurrence-free survival.
A total 951 patients were randomly assigned to ipilimumab (n=475) or placebo (n=476) between July 10, 2008, and Aug 1, 2011. The researchers found there were 528 recurrence-free survival events (234 in the ipilimumab arm compared to 294 in the placebo arm) with a median follow-up of 2.74 years. The researchers reported that the median recurrence-free survival was 26.1 months in the ipilimumab arm compared to 17.1 months in the placebo arm. The 3-year recurrence-free survival was 46.5% in the ipilimumab arm compared to 34.8% in the placebo arm.
The researchers found that the most common grade 3/4 immune-related adverse events in the ipilimumab group were gastrointestinal (16% compare to <1% in the placebo arm), hepatic adverse events (11% compared to <1% in the placebo arm), and endocrine (8% compared to 0% in the placebo arm). Dr. Eggermont and colleagues reported that adverse events led to discontinuation of treatment in 245 of 471 patients (52%) who started ipilimumab during the initial treatment period of four doses. During the study period, five patients died (1%) due to drug-related adverse events. Among these five patients, three died of colitis, one died from myocarditis, and one from multiple organ failure with Guillain-BarrÃ© syndrome.
This trial is ongoing and the authors write that the “risk–benefit ratio of adjuvant ipilimumab at this dose and schedule requires additional assessment based on distant metastasis-free survival, and overall survival endpoints to define its definitive value.”