Adjuvant interferon-α for the treatment of high-risk melanoma: an individual patient data meta-analysis

International Melanoma Meta-Analysis Collaborative Group (IMMCG), Natalie Ives, Stefan Suciu, Alexander M. Eggermont, John M. Kirkwood, Paul Lorigan, Svetomir Markovic, Claus Garbe, Keith Wheatley

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Background: Many randomised trials assessing interferon-α (IFN α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN α, an individual patient data (IPD) meta-analysis of these trials was undertaken.MethodsIPD was sought from all randomised trials of adjuvant IFN α versus no IFN α for high-risk melanoma. Primary outcomes were event-free survival (EFS) and overall survival (OS). Standard methods for quantitative IPD meta-analysis were used. Subgroup analyses by dose, duration of treatment, and various patient and disease-specific parameters were performed.Findings: Fifteen trials were included in the analysis (eleven with IPD). EFS was significantly improved with IFN α (Hazard Ratio (HR)=0·86, CI 0·81-0·91; P<0·00001), as was OS (HR=0·90, CI 0·85-0·97; P=0·003). The absolute differences in EFS at five and ten years were 3·5% and 2·7%, and for OS were 3·0% and 2·8% respectively in favour of IFN α. There was no evidence that the benefit of IFN-α differed depending on dose or duration of treatment, or by age, gender, site of primary tumour, disease stage, Breslow thickness, or presence of clinical nodes. Only for ulceration was there evidence of an interaction (test for heterogeneity: P=0·04 for EFS; P=0·002 for OS); only patients with ulcerated tumours appeared to obtain benefit from IFN α.Conclusion: This meta-analysis provides clear evidence that adjuvant IFN α significantly reduces the risk of relapse and improves survival, and shows no benefit for higher doses. The increased benefit in patients with ulcerated tumours, and lack of benefit in patients without ulceration, needs further investigation.Key Words: Individual patient data meta-analysis; randomised controlled trials; melanoma; adjuvant interferon.
Original languageEnglish
Pages (from-to)171-183
JournalEuropean Journal of Cancer
Early online date7 Jul 2017
Publication statusPublished - Sept 2017


  • Individual patient data meta-analysis
  • randomised controlled trials
  • melanoma
  • adjuvant interferon


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