title: Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macrometastatic nodes: an open-label, randomised, phase 3 European Association for Dermato-Oncology (EADO) study.
abstract: OBJECTIVE
  Both low-dose interferon (IFN) alfa-2b and pegylated interferon (Peg-IFN) alfa-2b have been shown to be superior to observation in the adjuvant treatment of melanoma without macrometastatic nodes, but have never been directly compared. Peg-IFN facilitates prolongation of treatment, which could provide additional benefit. This multicentre, open-label, randomised, phase 3 trial compared standard low-dose interferon IFN and prolonged treatment with Peg-IFN.
  
  
  METHODS
  Patients with resected melanoma ≥1.5mm thick and without clinically detectable node metastases were randomised 1:1 to treatment with IFN 3 MU subcutaneously (SC) three times weekly for 18 months or Peg-IFN 100 μg SC once weekly for 36 months. Sentinel lymph node dissection (SLND) was optional. The primary endpoint was disease-free survival (DFS). Secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS) and adverse events (AEs) grade 3-4.
  
  
  RESULTS
  Of 898 patients enrolled, 896 (443 Peg-IFN, 453 IFN) were eligible for evaluation (median follow-up 4.7 years). SLND was performed in 68.2% of patients. There were no statistical differences between the two arms for the primary outcome of DFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.73-1.15) or the secondary outcomes of DMFS (HR 1.02, 95% CI 0.80-1.32) and OS (HR 1.09, 95% CI 0.82-1.45). Peg-IFN was associated with higher rates of grade 3-4 AEs (47.3% versus 25.2%; p<0.0001) and discontinuations (54.3% versus 30.4%) compared with IFN.
  
  
  CONCLUSIONS
  This trial did not show superiority for adjuvant Peg-IFN over conventional low-dose IFN in melanoma patients without clinically detectable nodes. ClinicalTrials.gov identifier: NCT00221702.
authors.affiliation: Aix-Marseille University, CRO2, Service de Dermatologie, Hopital de Timone, 264 Rue St Pierre, 13885 Marseille CEDEX 05, Marseille, France. jean-jacques.grob@ap-hm.fr
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Grob
authors.forename: Thomas
authors.initials: T
authors.lastname: Jouary
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dréno
authors.forename: Julien
authors.initials: J
authors.lastname: Asselineau
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.forename: Marie Thérèse
authors.initials: MT
authors.lastname: Leccia
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.forename: Bruno
authors.initials: B
authors.lastname: Sassolas
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Herbst
authors.forename: Bernard
authors.initials: B
authors.lastname: Guillot
authors.forename: Genevieve
authors.initials: G
authors.lastname: Chene
authors.forename: Hubert
authors.initials: H
authors.lastname: Pehamberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b