Adjuvant ipilimumab in stage III melanoma: New landscape, new questions

Abstract

The recently reported significant prolongation of overall survival with ipilimumab as adjuvant in high-risk stage III melanoma patients represents an important event in the adjuvant treatment landscape. The European Organisation for Research and Treatment of Cancer 18071 trial demonstrated a 28% reduction in risk of death in patients treated with ipilimumab at 10 mg/kg (hazard ratio for death, 0.72; 95.1% CI, 0.58-0.88; P = 0.001) compared with placebo. All end-points-recurrence-free survival (RFS), distant-metastasis-free survival (DMFS) and overall survival (OS)-showed similar benefits. Survival rates at 5 years in ipilimumab-treated patients were OS 11%, DMFS 9% and RFS 11% higher than in placebo-treated patients. Global Health quality-of-life scores were not significantly different between treatment arms, in spite of significant adverse event rates that resulted in only 42% of patients receiving more than four doses of ipilimumab and only 28.9% of patients going beyond 1 year of treatment. Grades 3-4 immune-related adverse events occurred in 41.6% of ipilimumab-treated patients and in 2.7% of placebo-treated patients. One can speculate on dose and duration of treatment, as well as on the requirement for complete lymph-node dissection in sentinel-node-positive patients. The remaining role of interferons will be discussed regarding differences in sensitivity profiles-such as in ulcerated melanoma versus non-ulcerated melanoma-and access to new drugs. Ongoing trials with targeted agents and with anti programmed cell death protein 1 (anti-PD-1) agents may bring significant additional results in the next few years that will redefine how we treat stage III patients. Overall, pricing of new treatments will determine access and whether patients will actually benefit from new treatment options.

Keywords: Adjuvant therapy; Ipilimumab; Melanoma; Randomised trials; Survival.