Alexander M M Eggermont1, Piotr Rutkowski2, Caroline Dutriaux3, Rainer Hofman-Wellenhof4, Peter Dziewulski5, Maria Marples6, Floren Grange7, Catherine Lok8, Elisabetta Pennachioli9, Caroline Robert10, Alexander C J van Akkooi11, Lars Bastholt12, Alessandro Minisini13, Ernest Marshall14, François Salès15, Jean-Jacques Grob16, Oliver Bechter17, Dirk Schadendorf18, Sandrine Marreaud19, Michal Kicinski20, Stefan Suciu21, Alessandro A E Testori22. 1. Prinses Maxima Centrum, Utrecht, the Netherlands. Electronic address: alexander.eggermont@prinsesmaximacentrum.nl. 2. Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. Electronic address: piotr.rutkowski@pib-nio.pl. 3. CHU de Bordeaux, Groupe Hospitalier Saint-André, Hopital Saint-André, Bordeaux, France. Electronic address: caroline.dutriaux@chu-bordeaux.fr. 4. Medical University of Graz, Graz, Austria. Electronic address: rainer.hofmann@medunigraz.at. 5. Mid Essex Hospitals, Broomfield Hospital, Broomfield, United Kingdom. Electronic address: peter.dziewulski@meht.nhs.uk. 6. Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Leeds, United Kingdom. Electronic address: maria.marples@nhs.net. 7. CHU de Reims, Hôpital Robert Debré, Reims, France. Electronic address: fgrange@chu-reims.fr. 8. CHU Amiens, Hopital Sud, Amiens, France. Electronic address: lok.catherine@chu-amiens.fr. 9. Istituto Europeo di Oncologia, Milan, Italy. Electronic address: elisabetta.pennacchioli@ieo.it. 10. Gustave Roussy, Villejuif & Paris-Saclay University, Saint-Aubin, France. Electronic address: caroline.robert@gustaveroussy.fr. 11. Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, the Netherlands. Electronic address: a.v.akkooi@nki.nl. 12. Odense University Hospital, Odense, Denmark. Electronic address: lars.bastholt@rsyd.dk. 13. Azienda Sanitaria Universitaria Del Friuli Centrale, Udine, Italy. Electronic address: alessandro.minisini@asufc.sanita.fvg.it. 14. St Helens & Knowsley NHS Trust, Whiston Hospital, Prescot, United Kingdom. Electronic address: emarshall@nhs.net. 15. Institut Jules Bordet-Hopital Universitaire ULB, Brussels, Belgium. Electronic address: fsales@bordet.be. 16. Assistance Publique, Hopitaux de Marseille, Hôpital de La Timone (APHM), Marseille, France. Electronic address: jean-jacques.grob@ap-hm.fr. 17. Department of General Medical Oncology, University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium. Electronic address: oliver.bechter@uzleuven.be. 18. University Hospital Essen, Essen & German Cancer Consortium, Heidelberg, Germany. Electronic address: dirk.schadendorf@uk-essen.de. 19. EORTC Headquarters, Brussels, Belgium. Electronic address: sandrine.marreaud@eortc.org. 20. EORTC Headquarters, Brussels, Belgium. Electronic address: michal.kicinski@eortc.org. 21. EORTC Headquarters, Brussels, Belgium. Electronic address: stefan.suciu@eortc.org. 22. Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address: A.Testori@smatteo.pv.it.
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.
RCT Entities:
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.
Authors: Alexander M M Eggermont; Christian U Blank; Mario Mandala; Georgina V Long; Victoria G Atkinson; Stéphane Dalle; Andrew M Haydon; Andrey Meshcheryakov; Adnan Khattak; Matteo S Carlino; Shahneen Sandhu; James Larkin; Susana Puig; Paolo A Ascierto; Piotr Rutkowski; Dirk Schadendorf; Rutger Koornstra; Leonel Hernandez-Aya; Anna Maria Di Giacomo; Alfonsus J M van den Eertwegh; Jean-Jacques Grob; Ralf Gutzmer; Rahima Jamal; Paul C Lorigan; Alexander C J van Akkooi; Clemens Krepler; Nageatte Ibrahim; Sandrine Marreaud; Michal Kicinski; Stefan Suciu; Caroline Robert Journal: J Clin Oncol Date: 2020-09-18 Impact factor: 44.544