TY - JOUR
T1 - Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma
T2 - final results of EORTC 18991, a randomised phase III trial
AU - Eggermont, Alexander MM
AU - Suciu, Stefan
AU - Santinami, Mario
AU - Testori, Alessandro
AU - Kruit, Wim HJ
AU - Marsden, Jeremy
AU - Punt, Cornelis JA
AU - Salès, François
AU - Gore, Martin
AU - MacKie, Rona
AU - Kusic, Zvonko
AU - Dummer, Reinhard
AU - Hauschild, Axel
AU - Musat, Elena
AU - Spatz, Alain
AU - Keilholz, Ulrich
N1 - Funding Information:
We thank the investigators who participated to this study, the previous EORTC medical physicians (K Stoitchkov and F Lehmann), EORTC data managers (I Jagiello, C Spirlet, J de Wever, L Polders, L Meert, L De Smet, R Nossent), EORTC project managers (A Allgeier and K Engelen), and the overall project supervisor (A Marinus). We also thank the UK National Cancer Research Network and the Swiss Organization for Clinical Cancer Research for their longstanding cooperation and interaction with the EORTC in the conduct of EORTC trials. The EORTC 18991 trial was done with the financial support of Schering Plough Research International, who also provided the study drug for free.
PY - 2008
Y1 - 2008
N2 - Background: Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability. Methods: 1256 patients with resected stage III melanoma were randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627) 6 μg/kg per week for 8 weeks (induction) then 3 μg/kg per week (maintenance) for an intended duration of 5 years. Randomisation was stratified for microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumour thickness, sex, and centre. Randomisation was done with a minimisation technique. The primary endpoint was recurrence-free survival. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00006249. Findings: All randomised patients were included in the primary efficacy analysis. 608 patients in the interferon group and 613 patients in the observation group were included in safety analyses. The median length of treatment with pegylated interferon alfa-2b was 12 (IQR 3·8-33·4) months. At 3·8 (3·2-4·2) years median follow-up, 328 recurrence events had occurred in the interferon group compared with 368 in the observation group (hazard ratio 0·82, 95% CI 0·71-0·96; p=0·01); the 4-year rate of recurrence-free survival was 45·6% (SE 2·2) in the interferon group and 38·9% (2·2) in the observation group. There was no difference in overall survival between the groups. Grade 3 adverse events occurred in 246 (40%) patients in the interferon group and 60 (10%) in the observation group; grade 4 adverse events occurred in 32 (5%) patients in the interferon group and 14 (2%) in the observation group. In the interferon group, the most common grade 3 or 4 adverse events were fatigue (97 patients, 16%), hepatotoxicity (66, 11%), and depression (39, 6%). Treatment with pegylated interferon alfa-2b was discontinued because of toxicity in 191 (31%) patients. Interpretation: Adjuvant pegylated interferon alfa-2b for stage III melanoma has a significant, sustained effect on recurrence-free survival. Funding: Schering Plough Research International.
AB - Background: Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability. Methods: 1256 patients with resected stage III melanoma were randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627) 6 μg/kg per week for 8 weeks (induction) then 3 μg/kg per week (maintenance) for an intended duration of 5 years. Randomisation was stratified for microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumour thickness, sex, and centre. Randomisation was done with a minimisation technique. The primary endpoint was recurrence-free survival. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00006249. Findings: All randomised patients were included in the primary efficacy analysis. 608 patients in the interferon group and 613 patients in the observation group were included in safety analyses. The median length of treatment with pegylated interferon alfa-2b was 12 (IQR 3·8-33·4) months. At 3·8 (3·2-4·2) years median follow-up, 328 recurrence events had occurred in the interferon group compared with 368 in the observation group (hazard ratio 0·82, 95% CI 0·71-0·96; p=0·01); the 4-year rate of recurrence-free survival was 45·6% (SE 2·2) in the interferon group and 38·9% (2·2) in the observation group. There was no difference in overall survival between the groups. Grade 3 adverse events occurred in 246 (40%) patients in the interferon group and 60 (10%) in the observation group; grade 4 adverse events occurred in 32 (5%) patients in the interferon group and 14 (2%) in the observation group. In the interferon group, the most common grade 3 or 4 adverse events were fatigue (97 patients, 16%), hepatotoxicity (66, 11%), and depression (39, 6%). Treatment with pegylated interferon alfa-2b was discontinued because of toxicity in 191 (31%) patients. Interpretation: Adjuvant pegylated interferon alfa-2b for stage III melanoma has a significant, sustained effect on recurrence-free survival. Funding: Schering Plough Research International.
UR - http://www.scopus.com/inward/record.url?scp=46749103710&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(08)61033-8
DO - 10.1016/S0140-6736(08)61033-8
M3 - Article
C2 - 18620949
AN - SCOPUS:46749103710
SN - 0140-6736
VL - 372
SP - 117
EP - 126
JO - Lancet
JF - Lancet
IS - 9633
ER -