Pegylated interferon alfa-2b a possible adjuvant treatment option for melanoma

Adjuvant pegylated interferon alfa-2b improved the recurrence-free survival in patients with stage III melanoma.

Researchers for the EORTC Melanoma Group randomly assigned 1,256 patients with resected disease to observation or pegylated interferon alfa-2b. Patients who received the treatment had an induction dose of 6 mcg/kg per week for eight weeks then a maintenance dose of 3 mcg/kg per week for a median of 12 months.

The groups were stratified for microscopic vs. macroscopic nodal involvement, number of positive nodes, ulceration and tumor thickness, sex and study center.

The four-year recurrence-free survival rate was 45.6% in the treatment group vs. 38.9% in the observation group. There was no difference in OS. Five percent of the patients in the treatment group experienced grade-4 adverse events vs. 2% in the observation group.

The most common grade-3 or -4 adverse events were fatigue, hepatotoxicity and depression. Thirty-one percent of the patients in the treatment group discontinued due to toxicity.

In an accompanying editorial, experts say that pegylated interferon alfa-2b may be a good alternative to high-dose interferon for some patients, specifically those with melanoma in their sentinel nodes and some patients with macroscopic nodal disease. However, they said the median follow-up of 3.8 years is “too short for final conclusions, especially about the N1 population of patients.” – by Emily Shafer

Lancet. 2008;372:117-126.

High-dose interferon-alfa has been established as the standard adjuvant therapy for patients with stage III melanoma. No other treatments have shown improvements in relapse-free survival. The toxicities associated with high-dose interferon are higher compared to pegylated interferon, so pegylated interferon may be a better option. This study was conducted in Europe. However, pegylated interferon is not FDA-approved and not available for our patients outside of studies in the United States.

For an adjuvant melanoma study, a minimal follow-up of five years is necessary to determine a survival benefit. In historical survival data for patients with stage III melanoma, five years is a major landmark. Patients who survive that length of time are likely to experience long-term survival. This paper shows that pegylated interferon improved the relapse-free survival, but the median follow-up is only 3.8 years; more time is needed for the data to become more mature.

Adjuvant high-dose interferon therapy is only given to patients for one year, but patients are at highest risk for recurrent disease in the first five years. Adjuvant pegylated interferon is given for five years after surgery, with less toxicity. Even though this dosing regimen may be viewed as an inconvenience by some, most patients with high risk of melanoma recurrence will not object to this therapy if it can protect them from relapse.

– Wen-Jen Hwu, MD, PhD

HemOnc Today Editorial Board member