Adjuvant therapy with pegylated interferon-alfa2b vs observation in stage II B/C patients with ulcerated primary: Results of the European Organisation for Research and Treatment of Cancer 18081 randomised trial

Alexander M.M. Eggermont, Piotr Rutkowski, Caroline Dutriaux, Rainer Hofman-Wellenhof, Peter Dziewulski, Maria Marples, Floren Grange, Catherine Lok, Elisabetta Pennachioli, Caroline Robert, Alexander C.J. van Akkooi, Lars Bastholt, Alessandro Minisini, Ernest Marshall, François Salès, Jean Jacques Grob, Oliver Bechter, Dirk Schadendorf, Sandrine Marreaud, Michal KicinskiStefan Suciu, Alessandro A.E. Testori

Research output: Contribution to journalArticle

Abstract

Background: Subgroup analyses of two large EORTC adjuvant interferon-alpha2b (IFNα-2b) vs observation randomised trials demonstrated that a treatment benefit was observed only in patients with an ulcerated melanoma without palpable nodes (hazard ratio [HR] for recurrence-free survival [RFS] was 0.69). This was confirmed by a meta-analysis of 15 adjuvant IFN trials (HR: 0.79). Patients and methods: In the EORTC 18081 trial, sentinel node-negative stage II patients with an ulcerated primary melanoma were 1:1 randomised between pegylated (PEG)-IFNα-2b at 3 μg/kg/week subcutaneously and observation, for 2 years, or until disease recurrence or unacceptable toxicity in spite of dose adjustments to maintain an Eastern Cooperative Oncology Group performance status of 0 or 1. Main end-point was RFS. Secondary end-points included distant metastasis-free survival (DMFS), overall survival, and safety (EudraCT Number: 2009-010273-20). Results: Between February 2013 and January 2017, only 112 patients were randomised, 56 in each arm. The trial was stopped early for lack of recruitment. At a 3.4-year median follow-up, the estimated HR for the PEG-IFNα-2b group compared with the observation group regarding RFS was 0.66 (95% confidence interval [CI]: 0.32–1.37), and the 3-year RFS rate was 80.0% (95% CI: 65.7–88.8%) and 72.9% (95% CI: 58.3–83.0%), respectively. DMFS was prolonged: HR: 0.39 (95% CI: 0.15–0.97), and the 3-year DMFS rate was 90.6% (95% CI: 78.9–96.0%) vs 76.4% (95% CI: 62.1–85.9%). One patient in the PEG-IFNα-2b group died compared with 4 in the observation group. Fifty-four patients started PEG-IFNα-2b treatment, 16 (29%) completed 2 years of treatment, 2 (4%) stopped due to recurrence, 23 (43%) due to toxicity and 14 (25%) due to other reasons. Conclusions: The EORTC 18081 PEG-IFNα-2b randomised trial, observed a similar HR (0.69) for RFS as the previous EORTC trials (0.69). In countries without access to new drugs, adjuvant (PEG)-IFNα-2b treatment is an option for patients with ulcerated melanomas without palpable nodes.

Original languageEnglish
Pages (from-to)94-103
Number of pages10
JournalEuropean Journal of Cancer
Volume133
DOIs
Publication statusPublished - Jul 2020

Keywords

  • Adjuvant therapy
  • Pegylated interferon
  • Randomized trial
  • Stage II
  • Ulcerated melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Eggermont, A. M. M., Rutkowski, P., Dutriaux, C., Hofman-Wellenhof, R., Dziewulski, P., Marples, M., Grange, F., Lok, C., Pennachioli, E., Robert, C., van Akkooi, A. C. J., Bastholt, L., Minisini, A., Marshall, E., Salès, F., Grob, J. J., Bechter, O., Schadendorf, D., Marreaud, S., ... Testori, A. A. E. (2020). Adjuvant therapy with pegylated interferon-alfa2b vs observation in stage II B/C patients with ulcerated primary: Results of the European Organisation for Research and Treatment of Cancer 18081 randomised trial. European Journal of Cancer, 133, 94-103. https://doi.org/10.1016/j.ejca.2020.04.015