title: Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991.
abstract: Adjuvant interferon has modest activity in melanoma patients at high risk for relapse. Patient selection is important; stage and ulceration of the primary tumour are key prognostic factors.
  
  
  METHODS
  In this post hoc meta-analysis of European Organisation for Research and Treatment of Cancer (EORTC) trials 18952 (intermediate doses of interferon α-2b [IFN] versus observation in stage IIb-III patients) and 18991 (pegylated [PEG]-IFN versus observation in stage III patients), the predictive value of ulceration on the efficacy of IFN/PEG-IFN with regard to relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) was assessed in the overall population and in subgroups stratified by stage (IIb and III-N1 [microscopic nodal disease] and III-N2 [macroscopic nodal disease]).
  
  
  RESULTS
  In the overall population, the comparison of IFN/PEG-IFN versus observation for RFS, DMFS and OS yielded estimated hazard ratios (HR) of 0.85 (p = 0.004), 0.89 (p = 0.04) and 0.94 (p = 0.36), respectively. The impact of treatment was greater in the ulceration group (n = 849) compared with the non-ulceration group (n = 1336) for RFS (test for interaction: p = 0.02), DMFS (p < 0.001) and OS (p < 0.001). The greatest risk reductions were observed in patients with ulceration and stage IIb/III-N1, with estimated HR for RFS, DMFS, and OS of 0.69 (p = 0.003), 0.59 (p < 0.0001) and 0.58 (p < 0.0001), respectively. The efficacy of IFN/PEG-IFN was lower in stage III-N2 patients with ulceration and uniformly absent in patients without ulceration. There was consistency between the data of both trials.
  
  
  CONCLUSIONS
  This meta-analysis of the EORTC 18952 and 18991 trials indicated that both tumour stage and ulceration were predictive factors for the efficacy of adjuvant IFN/PEG-IFN therapy.
authors: Institut de Cancérologie Gustave Roussy, Villejuif, France. alexander.eggermont@igr.fr
authors: Alexander M M
authors: AM
authors: Eggermont
authors: Stefan
authors: S
authors: Suciu
authors: Alessandro
authors: A
authors: Testori
authors: Wim H
authors: WH
authors: Kruit
authors: Jeremy
authors: J
authors: Marsden
authors: Cornelis J
authors: CJ
authors: Punt
authors: Mario
authors: M
authors: Santinami
authors: François
authors: F
authors: Salès
authors: Dirk
authors: D
authors: Schadendorf
authors: Poulam
authors: P
authors: Patel
authors: Reinhard
authors: R
authors: Dummer
authors: Caroline
authors: C
authors: Robert
authors: Ulrich
authors: U
authors: Keilholz
authors: Antoine
authors: A
authors: Yver
authors: Alan
authors: A
authors: Spatz
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D014456:Ulcer / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a