Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis (EJC Vol 82, Sep2017, pp 171-183)

Natalie J. Ives, Stefan Suciu, Alexander M. M. Eggermont, John Kirkwood, Paul Lorigan, Svetomir N. Markovic, Claus Garbe, Keith Wheatley

Research output: Contribution to journalReview articlepeer-review


Abstract 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. Methods IPD 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 5 and 10 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 compared to lower doses. The increased benefit in patients with ulcerated tumours, and lack of benefit in patients without ulceration, needs further investigation.
Original languageEnglish
Article numberj.ejca.2017.06.006
Pages (from-to)171-183
Number of pages1
JournalEuropean Journal of Cancer
Early online date7 Jul 2017
Publication statusPublished - Sept 2017


  • Individual patient data meta-analysis
  • Randomised controlled trials
  • Melanoma
  • Adjuvant interferon

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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