Alexander M M Eggermont1, Stefan Suciu2, Piotr Rutkowski3, Willem H Kruit4, Cornelis J Punt5, Reinhard Dummer6, François Salès7, Ulrich Keilholz8, Gaetan de Schaetzen2, Alessandro Testori9. 1. Gustave Roussy Cancer Campus Grand Paris, Villejuif, France. Electronic address: alexander.eggermont@gustaveroussy.fr. 2. EORTC Headquarters, Brussels, Belgium. 3. Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland. 4. Erasmus MC Cancer Institute - Location Daniel den Hoed, Rotterdam, The Netherlands. 5. Academisch Medisch Centrum - Universiteit van Amsterdam, Amsterdam, The Netherlands. 6. Universitaetsspital Zurich, Zürich, Switzerland. 7. Institut Jules Bordet, Brussels, Belgium. 8. Charité, Berlin, Germany. 9. Istituto Europeo di Oncologia, Milan, Italy.
Abstract
BACKGROUND: We report on the long term outcome of the EORTC 18952 adjuvant interferon (IFN) trial in 1388 resected stage IIB/III melanoma patients and identify key predictive factors for outcome. METHODS: We analysed outcome of the EORTC 18952 trial (4 weeks of IFN, 10 MU, 5 times/week for 4 weeks followed by 12 months IFN at 10 MU, 3 times/week versus followed by 24 months IFN at 5 MU 3 times/week versus observation) regarding relapse-free survival (RFS), distant metastasis-free interval/survival (DMFI/DMFS), and overall survival (OS), and analysed potential predictive factors of outcome. FINDINGS: At a median follow-up of 11 years, the comparison of IFN 13 months versus IFN 25 months versus observation yielded estimated hazard ratios (HR) for RFS of 0.94 versus 0.84 (p = 0.06); for DMFI 0.95 versus 0.82 (p = 0.027); for DMFS 0.95 versus 0.84 (p = 0.07); and for OS 0·95 versus 0.84 (p = 0.08), respectively. The impact of treatment was greatest in the ulceration group, whereas in patients with non-ulcerated primaries the impact was null (HR ≥ 1.0). In patients with ulcerated melanoma the HR for IFN 13 months versus 25 months versus observation were for: RFS 0.82 (p = 0.16) versus 0.61 (p = 0.0008); DMFS 0.76 (p = 0.06) versus 0.57 (p = 0.0003); OS 0.80 (p = 0.13) versus 0.59 (p = 0.0007). In stage IIB/III-N1 (microscopic nodal involvement only) patients with ulcerated melanoma the HR estimates were for: RFS 0.85 versus 0.62; DMFS 0.80 versus 0.56; OS 0.77 versus 0.54. CONCLUSIONS: This long term report of the EORTC 18952 trial demonstrates the superiority of the 25-month IFN schedule and defines ulceration of the primary as the overriding predictive factor for IFN-sensitivity.
RCT Entities:
BACKGROUND: We report on the long term outcome of the EORTC 18952 adjuvant interferon (IFN) trial in 1388 resected stage IIB/III melanomapatients and identify key predictive factors for outcome. METHODS: We analysed outcome of the EORTC 18952 trial (4 weeks of IFN, 10 MU, 5 times/week for 4 weeks followed by 12 months IFN at 10 MU, 3 times/week versus followed by 24 months IFN at 5 MU 3 times/week versus observation) regarding relapse-free survival (RFS), distant metastasis-free interval/survival (DMFI/DMFS), and overall survival (OS), and analysed potential predictive factors of outcome. FINDINGS: At a median follow-up of 11 years, the comparison of IFN 13 months versus IFN 25 months versus observation yielded estimated hazard ratios (HR) for RFS of 0.94 versus 0.84 (p = 0.06); for DMFI 0.95 versus 0.82 (p = 0.027); for DMFS 0.95 versus 0.84 (p = 0.07); and for OS 0·95 versus 0.84 (p = 0.08), respectively. The impact of treatment was greatest in the ulceration group, whereas in patients with non-ulcerated primaries the impact was null (HR ≥ 1.0). In patients with ulcerated melanoma the HR for IFN 13 months versus 25 months versus observation were for: RFS 0.82 (p = 0.16) versus 0.61 (p = 0.0008); DMFS 0.76 (p = 0.06) versus 0.57 (p = 0.0003); OS 0.80 (p = 0.13) versus 0.59 (p = 0.0007). In stage IIB/III-N1 (microscopic nodal involvement only) patients with ulcerated melanoma the HR estimates were for: RFS 0.85 versus 0.62; DMFS 0.80 versus 0.56; OS 0.77 versus 0.54. CONCLUSIONS: This long term report of the EORTC 18952 trial demonstrates the superiority of the 25-month IFN schedule and defines ulceration of the primary as the overriding predictive factor for IFN-sensitivity.
Authors: Alexander M M Eggermont; Vanna Chiarion-Sileni; Jean-Jacques Grob; Reinhard Dummer; Jedd D Wolchok; Henrik Schmidt; Omid Hamid; Caroline Robert; Paolo A Ascierto; Jon M Richards; Céleste Lebbé; Virginia Ferraresi; Michael Smylie; Jeffrey S Weber; Michele Maio; Lars Bastholt; Laurent Mortier; Luc Thomas; Saad Tahir; Axel Hauschild; Jessica C Hassel; F Stephen Hodi; Corina Taitt; Veerle de Pril; Gaetan de Schaetzen; Stefan Suciu; Alessandro Testori Journal: N Engl J Med Date: 2016-10-07 Impact factor: 91.245
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