Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma

Alexander M M Eggermont, Stefan Suciu, Alessandro Testori, Mario Santinami, Wim H J Kruit, Jeremy Marsden, Cornelis J A Punt, François Salès, Reinhard Dummer, Caroline Robert, Dirk Schadendorf, Poulam M. Patel, Gaetan De Schaetzen, Alan Spatz, Ulrich Keilholz

Research output: Contribution to journalArticle

Abstract

Purpose: Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. Patients and Methods: In all, 1,256 patients with resected stage III melanoma were randomly assigned to observation (n = 629) or PEG-IFN-α-2b (n = 627) for an intended duration of 5 years. Stratification factors were microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumor thickness, sex, and center. Recurrence-free survival (RFS; primary end point), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed for the intent-totreat population. Results: At 7.6 years median follow-up, 384 recurrences or deaths had occurred with PEG-IFN-α-2b versus 406 in the observation group (hazard ratio [HR], 0.87; 95% CI, 0.76 to 1.00; P = .055); 7-year RFS rate was 39.1% versus 34.6%. There was no difference in OS (P = .57). In stage III-N1 ulcerated melanoma, RFS (HR, 0.72; 99% CI, 0.46 to 1.13; P = .06), DMFS (HR, 0.65; 99% CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99% CI, 0.35 to 0.97; P = .006) were prolonged with PEG-IFN-α-2b. PEG-IFN-α-2b was discontinued for toxicity in 37% of patients. Conclusion: Adjuvant PEG-IFN-α-2b for stage III melanoma had a positive impact on RFS, which was marginally significant and slightly diminished versus the benefit seen at prior follow-up (median, 3.8 years). No significant increase in DMFS or OS was noted in the overall population. Patients with ulcerated melanoma and lower disease burden had the greatest benefit.

Original languageEnglish
Pages (from-to)3810-3818
Number of pages9
JournalJournal of Clinical Oncology
Volume30
Issue number31
DOIs
Publication statusPublished - Nov 1 2012

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Melanoma
Observation
Survival
Therapeutics
Neoplasm Metastasis
Recurrence
peginterferon alfa-2b
Population
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. / Eggermont, Alexander M M; Suciu, Stefan; Testori, Alessandro; Santinami, Mario; Kruit, Wim H J; Marsden, Jeremy; Punt, Cornelis J A; Salès, François; Dummer, Reinhard; Robert, Caroline; Schadendorf, Dirk; Patel, Poulam M.; De Schaetzen, Gaetan; Spatz, Alan; Keilholz, Ulrich.

In: Journal of Clinical Oncology, Vol. 30, No. 31, 01.11.2012, p. 3810-3818.

Research output: Contribution to journalArticle

Eggermont, AMM, Suciu, S, Testori, A, Santinami, M, Kruit, WHJ, Marsden, J, Punt, CJA, Salès, F, Dummer, R, Robert, C, Schadendorf, D, Patel, PM, De Schaetzen, G, Spatz, A & Keilholz, U 2012, 'Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma', Journal of Clinical Oncology, vol. 30, no. 31, pp. 3810-3818. https://doi.org/10.1200/JCO.2011.41.3799
Eggermont, Alexander M M ; Suciu, Stefan ; Testori, Alessandro ; Santinami, Mario ; Kruit, Wim H J ; Marsden, Jeremy ; Punt, Cornelis J A ; Salès, François ; Dummer, Reinhard ; Robert, Caroline ; Schadendorf, Dirk ; Patel, Poulam M. ; De Schaetzen, Gaetan ; Spatz, Alan ; Keilholz, Ulrich. / Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 31. pp. 3810-3818.
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abstract = "Purpose: Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. Patients and Methods: In all, 1,256 patients with resected stage III melanoma were randomly assigned to observation (n = 629) or PEG-IFN-α-2b (n = 627) for an intended duration of 5 years. Stratification factors were microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumor thickness, sex, and center. Recurrence-free survival (RFS; primary end point), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed for the intent-totreat population. Results: At 7.6 years median follow-up, 384 recurrences or deaths had occurred with PEG-IFN-α-2b versus 406 in the observation group (hazard ratio [HR], 0.87; 95{\%} CI, 0.76 to 1.00; P = .055); 7-year RFS rate was 39.1{\%} versus 34.6{\%}. There was no difference in OS (P = .57). In stage III-N1 ulcerated melanoma, RFS (HR, 0.72; 99{\%} CI, 0.46 to 1.13; P = .06), DMFS (HR, 0.65; 99{\%} CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99{\%} CI, 0.35 to 0.97; P = .006) were prolonged with PEG-IFN-α-2b. PEG-IFN-α-2b was discontinued for toxicity in 37{\%} of patients. Conclusion: Adjuvant PEG-IFN-α-2b for stage III melanoma had a positive impact on RFS, which was marginally significant and slightly diminished versus the benefit seen at prior follow-up (median, 3.8 years). No significant increase in DMFS or OS was noted in the overall population. Patients with ulcerated melanoma and lower disease burden had the greatest benefit.",
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T1 - Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma

AU - Eggermont, Alexander M M

AU - Suciu, Stefan

AU - Testori, Alessandro

AU - Santinami, Mario

AU - Kruit, Wim H J

AU - Marsden, Jeremy

AU - Punt, Cornelis J A

AU - Salès, François

AU - Dummer, Reinhard

AU - Robert, Caroline

AU - Schadendorf, Dirk

AU - Patel, Poulam M.

AU - De Schaetzen, Gaetan

AU - Spatz, Alan

AU - Keilholz, Ulrich

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Purpose: Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. Patients and Methods: In all, 1,256 patients with resected stage III melanoma were randomly assigned to observation (n = 629) or PEG-IFN-α-2b (n = 627) for an intended duration of 5 years. Stratification factors were microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumor thickness, sex, and center. Recurrence-free survival (RFS; primary end point), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed for the intent-totreat population. Results: At 7.6 years median follow-up, 384 recurrences or deaths had occurred with PEG-IFN-α-2b versus 406 in the observation group (hazard ratio [HR], 0.87; 95% CI, 0.76 to 1.00; P = .055); 7-year RFS rate was 39.1% versus 34.6%. There was no difference in OS (P = .57). In stage III-N1 ulcerated melanoma, RFS (HR, 0.72; 99% CI, 0.46 to 1.13; P = .06), DMFS (HR, 0.65; 99% CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99% CI, 0.35 to 0.97; P = .006) were prolonged with PEG-IFN-α-2b. PEG-IFN-α-2b was discontinued for toxicity in 37% of patients. Conclusion: Adjuvant PEG-IFN-α-2b for stage III melanoma had a positive impact on RFS, which was marginally significant and slightly diminished versus the benefit seen at prior follow-up (median, 3.8 years). No significant increase in DMFS or OS was noted in the overall population. Patients with ulcerated melanoma and lower disease burden had the greatest benefit.

AB - Purpose: Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. Patients and Methods: In all, 1,256 patients with resected stage III melanoma were randomly assigned to observation (n = 629) or PEG-IFN-α-2b (n = 627) for an intended duration of 5 years. Stratification factors were microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumor thickness, sex, and center. Recurrence-free survival (RFS; primary end point), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed for the intent-totreat population. Results: At 7.6 years median follow-up, 384 recurrences or deaths had occurred with PEG-IFN-α-2b versus 406 in the observation group (hazard ratio [HR], 0.87; 95% CI, 0.76 to 1.00; P = .055); 7-year RFS rate was 39.1% versus 34.6%. There was no difference in OS (P = .57). In stage III-N1 ulcerated melanoma, RFS (HR, 0.72; 99% CI, 0.46 to 1.13; P = .06), DMFS (HR, 0.65; 99% CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99% CI, 0.35 to 0.97; P = .006) were prolonged with PEG-IFN-α-2b. PEG-IFN-α-2b was discontinued for toxicity in 37% of patients. Conclusion: Adjuvant PEG-IFN-α-2b for stage III melanoma had a positive impact on RFS, which was marginally significant and slightly diminished versus the benefit seen at prior follow-up (median, 3.8 years). No significant increase in DMFS or OS was noted in the overall population. Patients with ulcerated melanoma and lower disease burden had the greatest benefit.

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