title: Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma.
abstract: OBJECTIVE
  Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial.
  
  
  METHODS
  In all, 1,256 patients with resected stage III melanoma were randomly assigned to observation (n = 629) or PEG-IFN-α-2b (n = 627) for an intended duration of 5 years. Stratification factors were microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumor thickness, sex, and center. Recurrence-free survival (RFS; primary end point), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed for the intent-to-treat population.
  
  
  RESULTS
  At 7.6 years median follow-up, 384 recurrences or deaths had occurred with PEG-IFN-α-2b versus 406 in the observation group (hazard ratio [HR], 0.87; 95% CI, 0.76 to 1.00; P = .055); 7-year RFS rate was 39.1% versus 34.6%. There was no difference in OS (P = .57). In stage III-N1 ulcerated melanoma, RFS (HR, 0.72; 99% CI, 0.46 to 1.13; P = .06), DMFS (HR, 0.65; 99% CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99% CI, 0.35 to 0.97; P = .006) were prolonged with PEG-IFN-α-2b. PEG-IFN-α-2b was discontinued for toxicity in 37% of patients.
  
  
  CONCLUSIONS
  Adjuvant PEG-IFN-α-2b for stage III melanoma had a positive impact on RFS, which was marginally significant and slightly diminished versus the benefit seen at prior follow-up (median, 3.8 years). No significant increase in DMFS or OS was noted in the overall population. Patients with ulcerated melanoma and lower disease burden had the greatest benefit.
authors.affiliation: Institute de Cancérologie Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, Paris-Sud, France. alexander.eggermont@igr.fr
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
authors.forename: Wim H J
authors.initials: WH
authors.lastname: Kruit
authors.forename: Jeremy
authors.initials: J
authors.lastname: Marsden
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: François
authors.initials: F
authors.lastname: Salès
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.forename: Poulam M
authors.initials: PM
authors.lastname: Patel
authors.forename: Gaetan
authors.initials: G
authors.lastname: de Schaetzen
authors.forename: Alan
authors.initials: A
authors.lastname: Spatz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; 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 / Q000601:surgery*; D055815:Young Adult
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b