TY - JOUR
T1 - Adjuvant therapy with pegylated interferon-alfa2b vs observation in stage II B/C patients with ulcerated primary
T2 - Results of the European Organisation for Research and Treatment of Cancer 18081 randomised trial
AU - Eggermont, Alexander M M
AU - Rutkowski, Piotr
AU - Dutriaux, Caroline
AU - Hofman-Wellenhof, Rainer
AU - Dziewulski, Peter
AU - Marples, Maria
AU - Grange, Floren
AU - Lok, Catherine
AU - Pennachioli, Elisabetta
AU - Robert, Caroline
AU - van Akkooi, Alexander C J
AU - Bastholt, Lars
AU - Minisini, Alessandro
AU - Marshall, Ernest
AU - Salès, François
AU - Grob, Jean-Jacques
AU - Bechter, Oliver
AU - Schadendorf, Dirk
AU - Marreaud, Sandrine
AU - Kicinski, Michal
AU - Suciu, Stefan
AU - Testori, Alessandro A E
N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Chemotherapy, Adjuvant
KW - Combined Modality Therapy
KW - Drug Administration Schedule
KW - Europe/epidemiology
KW - Female
KW - Humans
KW - Injections, Subcutaneous
KW - Interferon alpha-2/administration & dosage
KW - Interferon-alpha/administration & dosage
KW - Male
KW - Medical Oncology/organization & administration
KW - Melanoma/complications
KW - Middle Aged
KW - Neoplasm Staging
KW - Polyethylene Glycols/administration & dosage
KW - Recombinant Proteins/administration & dosage
KW - Skin Neoplasms/complications
KW - Skin Ulcer/complications
KW - Societies, Medical/organization & administration
KW - Survival Analysis
KW - Watchful Waiting/methods
U2 - 10.1016/j.ejca.2020.04.015
DO - 10.1016/j.ejca.2020.04.015
M3 - Article
C2 - 32470710
SN - 0959-8049
VL - 133
SP - 94
EP - 103
JO - Eur. J. Cancer
JF - Eur. J. Cancer
ER -