CHICAGO, IL— Despite significant adverse events (AEs), including treatment-related deaths, adjuvant ipilimumab decreases the risk of advanced melanoma recurrence after surgery by 25%, according to findings from the phase 3 randomized, double-blind, placebo-controlled EORTC 18071 clinical trial, presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
“This is a promising treatment—we saw substantially fewer recurrences among patients who are at high risk of relapse,” concluded lead study author Alexander Eggermont, MD, PhD, Director General of the Gustave Roussy Cancer Campus Grande Paris in France.
Ipilimumab is a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, improving antitumor immune responses.
A total of 951 patients with surgically treated, high-risk stage III cutaneous melanoma were randomly assigned to receive placebo (n=476) or ipilimumab (n=475; 10 mg/kg every 3 weeks for four doses, then every 3 months for up to 3 years until completion, disease recurrence, or unacceptable toxicity). Patients were stratified by tumor stage (IIIA, IIIB, or IIIC) and lymph node involvement (number of nodes).
Eggermont, MD, PhD
At a median follow-up of 2.7 years, ipilimumab “significantly improved RFS [recurrence-free survival] versus placebo,” Dr. Eggermont reported.
The 3-year RFS rates were 46.5% for patients in the ipilimumab group, compared to 34.8% for placebo (median RFS, 26.1 months vs. 17.1 months; hazard ratio [HR], 0.75; 95% CI: 0.64-0.90; P = 0.0013).
However, 36.5% of patients in the ipilimumab group experienced grade 3 immune-related adverse events, and 5.5% experienced grade 4 immune-related AEs; five patients (1%) died as a result, Dr. Eggermont cautioned. Just under half (48%) of patients in the ipilimumab group discontinued treatment because of AEs. Grade 3/4 immune-related AEs included gastrointestinal (14.9% vs. 1.1% in placebo arm), hepatic (7.9% vs. 2.8%), and endocrine (7.9% vs. 0.6%). Hypophysitis was reported for 4.7% (grade 3) and 0.4% (grade 4) of patients.
RELATED: Skin Cancer Resource Center
“Most immune-related AEs were managed and resolved with established treatment algorithms,” Dr. Eggermont noted.
But immune-related autoimmune hepatitis and endocrinopathies such as hypophysitis may require long-term management, including hormone replacement therapy, he said.
“We’ve seen many impressive new treatments for advanced melanoma in recent years,” noted Dr. Eggermont. “This trial with ipilimumab is the first to show we may be able to give these new drugs earlier in the course of the disease, where they can do more good and potentially cure more patients.”
- Eggermont AM, Chiarion-Sileni V, Grob JJ et al. Abstract LBA9008. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.