Adjuvant interferon-α for the treatment of high-risk melanoma

An individual patient data meta-analysis

the International Melanoma Meta-Analysis Collaborative Group (IMMCG), the International Melanoma Meta-Analysis Collaborative Group (IMMCG)

Research output: Contribution to journalReview article

41 Citations (Scopus)

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 (US)
Pages (from-to)171-183
Number of pages13
JournalEuropean Journal of Cancer
Volume82
DOIs
StatePublished - Sep 1 2017

Fingerprint

Interferons
Meta-Analysis
Melanoma
Disease-Free Survival
Survival
Therapeutics
Neoplasms
Recurrence

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

the International Melanoma Meta-Analysis Collaborative Group (IMMCG), & the International Melanoma Meta-Analysis Collaborative Group (IMMCG) (2017). Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis. European Journal of Cancer, 82, 171-183. https://doi.org/10.1016/j.ejca.2017.06.006

Adjuvant interferon-α for the treatment of high-risk melanoma : An individual patient data meta-analysis. / the International Melanoma Meta-Analysis Collaborative Group (IMMCG); the International Melanoma Meta-Analysis Collaborative Group (IMMCG).

In: European Journal of Cancer, Vol. 82, 01.09.2017, p. 171-183.

Research output: Contribution to journalReview article

the International Melanoma Meta-Analysis Collaborative Group (IMMCG) & the International Melanoma Meta-Analysis Collaborative Group (IMMCG) 2017, 'Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis', European Journal of Cancer, vol. 82, pp. 171-183. https://doi.org/10.1016/j.ejca.2017.06.006
the International Melanoma Meta-Analysis Collaborative Group (IMMCG), the International Melanoma Meta-Analysis Collaborative Group (IMMCG). Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis. European Journal of Cancer. 2017 Sep 1;82:171-183. https://doi.org/10.1016/j.ejca.2017.06.006
the International Melanoma Meta-Analysis Collaborative Group (IMMCG) ; the International Melanoma Meta-Analysis Collaborative Group (IMMCG). / Adjuvant interferon-α for the treatment of high-risk melanoma : An individual patient data meta-analysis. In: European Journal of Cancer. 2017 ; Vol. 82. pp. 171-183.
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title = "Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis",
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.",
keywords = "Adjuvant interferon, Individual patient data meta-analysis, Melanoma, Randomised controlled trials",
author = "{the International Melanoma Meta-Analysis Collaborative Group (IMMCG)} and {the International Melanoma Meta-Analysis Collaborative Group (IMMCG)} and Ives, {Natalie J.} and Stefan Suciu and Eggermont, {Alexander M.M.} and John Kirkwood and Paul Lorigan and Markovic, {Svetomir N.} and Claus Garbe and Keith Wheatley and Rosaria Bufalino and David Cameron and Natale Cascinelli and Valerie Doherty and Alexander Eggermont and Claus Garbe and Martin Gore and Barry Hancock and Rebecca Harrison and Natalie Ives and John Kirkwood and Michael Kressig and Sandra Lee and Paul Lorigan and Rona MacKie and Markovic, {Svetomir Nenad} and Jerry Marsden and Stefan Suciu and Suman, {Vera Jean} and Lesley Turner and Keith Wheatley",
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T1 - Adjuvant interferon-α for the treatment of high-risk melanoma

T2 - An individual patient data meta-analysis

AU - the International Melanoma Meta-Analysis Collaborative Group (IMMCG)

AU - the International Melanoma Meta-Analysis Collaborative Group (IMMCG)

AU - Ives, Natalie J.

AU - Suciu, Stefan

AU - Eggermont, Alexander M.M.

AU - Kirkwood, John

AU - Lorigan, Paul

AU - Markovic, Svetomir N.

AU - Garbe, Claus

AU - Wheatley, Keith

AU - Bufalino, Rosaria

AU - Cameron, David

AU - Cascinelli, Natale

AU - Doherty, Valerie

AU - Eggermont, Alexander

AU - Garbe, Claus

AU - Gore, Martin

AU - Hancock, Barry

AU - Harrison, Rebecca

AU - Ives, Natalie

AU - Kirkwood, John

AU - Kressig, Michael

AU - Lee, Sandra

AU - Lorigan, Paul

AU - MacKie, Rona

AU - Markovic, Svetomir Nenad

AU - Marsden, Jerry

AU - Suciu, Stefan

AU - Suman, Vera Jean

AU - Turner, Lesley

AU - Wheatley, Keith

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

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KW - Individual patient data meta-analysis

KW - Melanoma

KW - Randomised controlled trials

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