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Randomized Controlled Trial
. 2020 Jul:133:94-103.
doi: 10.1016/j.ejca.2020.04.015. Epub 2020 May 26.

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  1 , Piotr Rutkowski  2 , Caroline Dutriaux  3 , Rainer Hofman-Wellenhof  4 , Peter Dziewulski  5 , Maria Marples  6 , Floren Grange  7 , Catherine Lok  8 , Elisabetta Pennachioli  9 , Caroline Robert  10 , Alexander C J van Akkooi  11 , Lars Bastholt  12 , Alessandro Minisini  13 , Ernest Marshall  14 , François Salès  15 , Jean-Jacques Grob  16 , Oliver Bechter  17 , Dirk Schadendorf  18 , Sandrine Marreaud  19 , Michal Kicinski  20 , Stefan Suciu  21 , Alessandro A E Testori  22
Affiliations
Randomized Controlled Trial

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 et al. Eur J Cancer. 2020 Jul.

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.

Keywords: Adjuvant therapy; Pegylated interferon; Randomized trial; Stage II; Ulcerated melanoma.

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Conflict of interest statement

Conflict of interest statement A.M.M.E. reports receiving personal fees as consultant advisor for Biocad, BioInvent, Bristol Myers Squibb (BMS), CatalYm, Ellipses, Glaxo Smith Kline (GSK), HalioDX, Incyte, IO Biotech, ISA Pharmaceuticals, Nektar, Merck Sharpe & Dohme (MSD), Novartis, Pfizer, Polynoma, Regeneron, Sanofi, Sellas, SkylineDx. P.R. reports receiving personal fees as consultant advisor for Novartis, MSD, BMS, Roche, Pfizer, Blueprint Medicines and Pierre Fabre, outside the submitted work. R.H.-W. reports receiving grants and non-financial support from EORTC, during the conduct of the study. C.R. reports personal fees as consultant advisor for Roche, Pierre Fabre, Merck, Novartis, Amgen, BMS, Novartis, MSD, Sanofi, Biothera, Ultimovacs, outside the submitted work. A.v.A. reports receiving grants from Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Sanofi and 4SC, outside the submitted work. L.B. reports receiving personal fees as consultant advisor for BMS, Novartis, MSD, Swedish Orphan, Bayer and Incyte outside the submitted work. A.M. reports receiving personal fees from Novartis, Pierre Fabre, MSD and SunPharma, outside the submitted work. J.J.G. reports receiving personal fees for advisory role from BMS, Novartis, MSD, Roche, Amgen,Pierre Fabre, Merck, Pfizer and Sanofi, and has also received travel support from BMS, Novartis, MSD, outside the submitted work. D.S. reports receiving grants, personal fees for consulting or advisory role; received honoraria; received travel expenses, accommodations, expenses from MSD, during the conduct of the study; and also received personal fees for consulting or advisory role; honoraria; travel expenses, accommodations, expenses from Roche / Genentech, personal fees, non-financial support and other from Novartis, grants and personal fees from BMS, personal fees and non-financial support from Merck Serono, and Amgen, personal fees from Immunocore, Incyte, 4SC, Pierre Fabre, Mologen, Sanofi / Regeneron, Roche, Sysmex, Agenus, Array BioPharma, AstraZeneca, InFlarX, Philogen, Nektar, Sandoz, non-financial support from Merck, outside the submitted work. M.M., F.G., E.P., E.M., O.B., S.M., M.K. and S.S. report no competing interests. A.A.E.T. reports receiving travel support from Agenus, outside the submitted work.

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