A chemically modified (pegylated) form of interferon alfa-2b improves recurrence-free survival (RFS) in melanoma patients compared with observation alone.
In this randomised, phase III study, published in The Lancet, Professor Alexander Eggermont, Erasmus University Medical Centre, Rotterdam, Netherlands and colleagues from the EORTC Melanoma Group aimed to determine whether pegylated interferon alfa-2b could facilitate prolonged exposure while maintaining tolerability.
The trial looked at 1256 patients with post-surgery stage III melanoma. 629 were assigned to observation, the other 627 to pegylated interferon alfa-2b 6 µ/kg body weight for 8 weeks (induction), then 3 µ/kg for an intended duration of five years (maintenance). The final analysis included 613 observation patients and 608 pegylated interferon alfa-2b patients. The median length of treatment with pegylated interferon alfa-2b was one year, and at median-follow up of just over three-and-a-half years, 328 recurrence events had occurred in pegylated interferon alfa-2b group and 368 in the observation group; thus pegylated interferon alfa-2b reduced the risk of recurrence by 18%, which became 15% after four years. There was no difference in overall survival between the groups.
Serious adverse events (grade 3) occurred in 246 (40%) of pegylated interferon alfa-2b patients and 60 (10%) observation patients, while grade 4 serious adverse events occurred in 32 (5%) of pegylated interferon alfa-2b patients and 14 (2%) of observation patients. In the pegylated interferon alfa-2b group, the most common grade 3 or 4 adverse events were fatigue (16% of patients) liver toxicity (11%), and depression (6%). Treatment with pegylated interferon alfa-2b was discontinued because of toxicity in 191 patients. The authors conclude: "The results of this large phase III study of adjuvant therapy in patients with stage III melanoma suggest that prolonged treatment with pegylated interferon alfa-2b significantly improves recurrence-free survival compared with observation alone."
In the accompanying Comment, Dr Vernon Sondak, H Lee Moffitt Cancer Centre and University of South Florida College of Medicine, Tampa, FL, USA, and Dr Lawrence Flaherty, Karmanos Institute and the Wayne State University School of Medicine, MI, USA, say RFS is an appropriate endpoint as many patients with melanoma are willing to accept significant toxicity in exchange for modest improvements in RFS, even in the absence of an overall survival effect. They conclude: "For the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon. Some patients with macroscopic nodal disease who would not tolerate or accept high-dose interferon will also want to consider this approach."