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

被引：9

作者：

Eggermont, Alexander M. M. ^{[1
]}

Rutkowski, Piotr ^{[2
]}

Dutriaux, Caroline ^{[3
]}

Hofman-Wellenhof, Rainer ^{[4
]}

Dziewulski, Peter ^{[5
]}

Marples, Maria ^{[6
]}

Grange, Floren ^{[7
]}

Lok, Catherine ^{[8
]}

Pennachioli, Elisabetta ^{[9
]}

Robert, Caroline ^{[10
,11
]}

van Akkooi, Alexander C. J. ^{[12
]}

Bastholt, Lars ^{[13
]}

Minisini, Alessandro ^{[14
]}

Marshall, Ernest ^{[15
]}

Sales, Francois ^{[16
]}

Grob, Jean-Jacques ^{[17
]}

Bechter, Oliver ^{[18
]}

Schadendorf, Dirk ^{[19
]}

Marreaud, Sandrine ^{[20
]}

Kicinski, Michal ^{[20
]}

Suciu, Stefan ^{[20
]}

Testori, Alessandro A. E. ^{[21
]}

机构：

[1] Prinses Maxima Ctr, Utrecht, Netherlands

[2] Maria Sklodowska Curie Natl Res Inst Oncol, Warsaw, Poland

[3] CHU Bordeaux, Grp Hosp St Andre, Hop St Andre, Bordeaux, France

[4] Med Univ Graz, Graz, Austria

[5] Broomfield Hosp, Mid Essex Hosp, Broomfield, England

[6] St James Univ Hosp, Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England

[7] CHU Reims, Hop Robert Debre, Reims, France

[8] CHU Amiens, Hop Sud, Amiens, France

[9] Ist Europeo Oncol, Milan, Italy

[10] Gustave Roussy, Villejuif, France

[11] Paris Saclay Univ, St Aubin, France

[12] Netherlands Canc Inst Antoni van Leeuwenhoek, Amsterdam, Netherlands

[13] Odense Univ, Odense, Denmark

[14] Azienda Sanit Univ Friuli Cent, Udine, Italy

[15] Whiston Hosp, St Helens & Knowsley NHS Trust, Prescot, England

[16] Hop Univ ULB, Inst Jules Bordet, Brussels, Belgium

[17] Hop La Timone, Assistance Publ Hop Marseille, Marseille, France

[18] Univ Hosp Leuven, Dept Gen Med Oncol, Campus Gasthuisberg, Leuven, Belgium

[19] Essen & German Canc Consortium, Univ Hosp Essen, Heidelberg, Germany

[20] EORTC Headquarters, Brussels, Belgium

[21] Fdn IRCCS Policlin San Matteo, Pavia, Italy

来源：

EUROPEAN JOURNAL OF CANCER | 2020年 / 133卷

关键词：

Ulcerated melanoma; Adjuvant therapy; Pegylated interferon; Randomized trial; Stage II; HIGH-RISK MELANOMA; TERM-FOLLOW-UP; CUTANEOUS MELANOMA; INTERDISCIPLINARY GUIDELINE; COMPLETE RESECTION; DOUBLE-BLIND; EORTC; 18952; IPILIMUMAB; ALPHA; PLACEBO;

D O I：

10.1016/j.ejca.2020.04.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Subgroup analyses of two large EORTC adjuvant interferon-alpha2b (IFN alpha-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)-IFN alpha-2b at 3 mu g/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-IFN alpha-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-IFN alpha-2b group died compared with 4 in the observation group. Fifty-four patients started PEG-IFN alpha-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-IFN alpha-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)-IFN alpha-2b treatment is an option for patients with ulcerated melanomas without palpable nodes. (C) 2020 Elsevier Ltd. All rights reserved.

引用

页码：94 / 103

页数：10

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