A chemically modified (pegylated*) form of interferon alfa-2b improves recurrence-free survival (RFS) in melanoma patients compared with observation alone, conclude authors of an Article in this week's edition of The Lancet. An accompanying Comment says this new form of interferon will be an attractive treatment option compared to existing interferon for many patients.
In this randomised, phase III study, Professor Alexander Eggermont, Erasmus University Medical Centre, Rotterdam, Netherlands and colleagues from the EORTC Melanoma Group aimed to determine whether pegylated interferon alfa-2b (PEG-IFN-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 PEG-IFN-2b at 6 μg / kg body weight for 8 weeks (induction), then 3 μg / kg for an intended duration of five years (maintenance). The final analysis included 613 observation patients and 608 PEG-IFN-2b patients. The median length of treatment with PEG-IFN-2b was one year, and at median-follow up of just over three-and-a-half years, 328 recurrence events had occurred in PEG-IFN-2b group and 368 in the observation group; thus PEG-IFN-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 PEG-IFN-2b patients and 60 (10%) observation patients, while grade 4 serious adverse events occurred in 32 (5%) of PEG-IFN-2b patients and 14 (2%) of observation patients. In the PEG-IFN-2b group, the most common grade 3 or 4 adverse events were fatigue (16% of patients) liver toxicity (11%), and depression (6%). Treatment with PEG-IFN-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."
Notes to editors: *pegylated interferon is the modified form of interferon (IFN) that prolongs the circulating time of IFN in the blood. This results in constant levels of IFN in the blood when injected subcutaneously once a week, whilst with regular IFN daily injections would have been necessary.
**The sentinel lymph node is the first lymph node which is contaminated by tumour cells
Professor Alexander Eggermont, Erasmus University Medical Centre, Rotterdam, Netherlands T) +31-654230633 E) a.m.m.eggermont@erasmusmc.nl
Dr Vernon Sondak, H Lee Moffitt Cancer Centre and University of South Florida College of Medicine, Tampa, FL, USA T) +1 (813) 745-1968 E) vernon.sondak@moffitt.org
http://multimedia.thelancet.com/pdf/press/melanoma.pdf
Journal
The Lancet