Adjuvant Ipilimumab Prolongs Survival in High-Risk Stage III Melanoma, Phase III Study Reports


Key Points

  • Ipilimumab significantly prolonged recurrence-free, overall, and distant metastasis–free survival in patients with high-risk stage III melanoma.
  • Ipilimumab was associated with a higher incidence of severe immune-related adverse events.

In the phase III European Organisation for Research and Treatment of Cancer (EORTC) trial 18071 reported at the recent European Society for Medical Oncology meeting and in The New England Journal of Medicine by Eggermont et al, adjuvant ipilimumab (Yervoy) was found to improve recurrence-free and overall survival vs placebo among patients with high-risk stage III melanoma. The trial supported the 2015 approval for ipilimumab in this setting.

Study Details

In the double-blind trial, 951 patients from 99 sites in 19 countries who had undergone complete resection of stage III cutaneous melanoma with regional lymph node involvement were randomized between July 2008 and August 2011 to receive ipilimumab at 10 mg/kg (n = 475 patients) or placebo (n  = 476) every 3 weeks for 4 doses and then every 3 months for up to 3 years or until disease recurrence or unacceptable toxicity. Patients with stage IIIA disease had to have at least one metastasis measuring > 1 mm in the greatest dimension. Recurrence-free survival was the primary endpoint.

Overall, patients had a median age of 51 to 52 years; 62% were male; disease stage was IIIA in 21%, IIIB in 38%, IIIC with 1 to 3 positive nodes in 25% to 26%, and stage IIIC with at least 4 positive nodes in 20% to 21%; and ulceration was present in 42%.

Survival Outcomes

Median follow-up was 5.3 years. At 5 years, recurrence-free survival was 40.8% in the ipilimumab group vs 30.3% in the placebo group (hazard ratio [HR] = 0.76, P < .001). Five-year rates were 65.4% vs 54.4% for overall survival (HR = 0.72, P = 0.001) and 48.3% vs 38.9% for distant metastasis–free survival (HR = 0.76, P = .002). At least 1 postprotocol treatment was received by 194 of the 264 patients in the ipilimumab group and 250 of 323 patients in the placebo group (including ipilimumab in 76 patients) who had recurrence or died.

Adverse Events

Adverse events of grade 3 or 4 occurred in 54.1% of the ipilimumab group vs 26.2% of the placebo group. Grade 3 or 4 immune-related adverse events occurred in 41.6% vs 2.7%, with the most common in the ipilimumab group being gastrointestinal events (16%) and hepatic events (11%). Five patients (1.1%) in the ipilimumab group died of immune-related adverse events.

The investigators concluded: “As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis–free survival than placebo. There were more immune-

related adverse events with ipilimumab than with placebo.

The study was funded by Bristol-Myers Squibb.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.