European Journal of Cancer
Volume 48, Issue 2 , Pages 218-225, January 2012

Ulceration and stage are predictive of interferon efficacy in melanoma: Results of the phase III adjuvant trials EORTC 18952 and EORTC 18991☆

  • Alexander M.M. Eggermont

      Affiliations

    • Institut de Cancérologie Gustave Roussy, Villejuif, France
    • Corresponding Author InformationCorresponding author: Address: Institut de Cancérologie Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif/Paris-Sud, France. Tel.: +33 1 42 11 40 16; fax: +33 1 42 11 52 52.
    • For the EORTC Melanoma Group.
    • ,
  • Stefan Suciu

      Affiliations

    • EORTC Headquarters, Brussels, Belgium
    • For the EORTC Melanoma Group.
    • ,
  • Alessandro Testori

      Affiliations

    • European Institute of Oncology, Milan, Italy
    • For the EORTC Melanoma Group.
    • ,
  • Wim H. Kruit

      Affiliations

    • Erasmus University Medical Center, Rotterdam, Netherlands
    • For the EORTC Melanoma Group.
    • ,
  • Jeremy Marsden

      Affiliations

    • University of Birmingham, Birmingham, United Kingdom
    • For the EORTC Melanoma Group.
    • ,
  • Cornelis J. Punt

      Affiliations

    • Nijmegen University Medical Center, Nijmegen, Netherlands
    • For the EORTC Melanoma Group.
    • ,
  • Mario Santinami

      Affiliations

    • National Cancer Institute Milan, Milan, Italy
    • For the EORTC Melanoma Group.
    • ,
  • François Salès

      Affiliations

    • Institut Jules Bordet, Brussels, Belgium
    • For the EORTC Melanoma Group.
    • ,
  • Dirk Schadendorf

      Affiliations

    • University Essen, Essen, Germany
    • For the EORTC Melanoma Group.
    • ,
  • Poulam Patel

      Affiliations

    • University of Nottingham, Nottingham, United Kingdom
    • For the EORTC Melanoma Group.
    • ,
  • Reinhard Dummer

      Affiliations

    • University of Zürich, Zürich, Switzerland
    • For the EORTC Melanoma Group.
    • ,
  • Caroline Robert

      Affiliations

    • Institut de Cancérologie Gustave Roussy, Villejuif, France
    • For the EORTC Melanoma Group.
    • ,
  • Ulrich Keilholz

      Affiliations

    • Charité, Berlin, Germany
    • For the EORTC Melanoma Group.
    • ,
  • Antoine Yver

      Affiliations

    • Schering Plough Research Institute, Kenilworth, NJ, USA
    • For the EORTC Melanoma Group.
    • ,
  • Alan Spatz

      Affiliations

    • McGill University, Montreal, Canada
    • For the EORTC Melanoma Group.

Received 28 September 2011; accepted 28 September 2011. published online 07 November 2011.

Abstract 

Summary

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]).

Findings

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.

Interpretation

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.

Keywords: Melanoma, Stage, Ulceration, Predictive Factors, Adjuvant Interferon Efficacy, Phase III Trials

 

☆ Presented in part by Alexander M.M. Eggermont at the 2009 Annual Meeting of American Society of Clinical Oncology (Proc Soc Am Clin Oncol 2009; 27: 9007. Abstract).

PII: S0959-8049(11)00787-8

doi:10.1016/j.ejca.2011.09.028

European Journal of Cancer
Volume 48, Issue 2 , Pages 218-225, January 2012

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