Long-term adjuvant therapy with pegylated interferon-alpha2b (Peg-IFN) improves relapse-free survival in patients with stage III melanoma compared with observation alone, according to results of a phase III study presented at the annual meeting of the American Society of Clinical Oncology.

European Organisation for Research and Treatment of Cancer (EORTC) Trial 18991, led by Alexander M. Eggermont, MD, PhD, of Erasmus University Medical Center, The Netherlands, was the largest adjuvant interferon trial held in this patient population.

The trial, conducted at centers in 17 countries, randomized 1256 patients to subcutaneous treatment with Peg-IFN for up to five years (induction of 6 μg/kg per week for a median of 8 weeks, followed by maintenance at 3 μg/kg per week for a median of 14.9 months) or observation. Among patients in the active arm, 23 percent received treatment for four or five years.

The difference in duration of relapse-free survival between arms was significant, with a median of 34.8 months for patients in the active arm and 25.5 months for patients in the observation arm.

Eggermont noted “We have never before seen this long a duration of benefit [of the hazard ratio over time] in an interferon trial.”

Looking at the entire population, there was no significant difference between arms in either distant metastasis-free survival or overall survival. However, patients with only microscopic nodal involvement (sentinel node-positive) seemed to have better outcomes, in terms of both relapse-free and distant metastasis-free survival. This subgroup of patients, which accounted for 43 percent of the total patient population, was responsible for the main outcome of the trial.

The investigators observed the usual interferon-related side effects among patients in the active arm. The most common grade 3 and 4 toxicities - fatigue, hepatotoxicity, and depression - did not worsen with longer treatment duration.

In response to a question from an audience member who asked whether Peg-IFN should be the standard therapy for patients with stage III melanoma, Eggermont responded that, “we don't have an argument against interferon for patients with N1 microscopic disease … this treatment should be seriously considered [in all patients with stage III melanoma]. Will the patient need 5 years of treatment? We don't know.”

He added that observation with no treatment should continue to be the control for patients with N2 palpable disease in future studies.