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EORTC 18991 phase III trial: Long-term adjuvant pegylated interferon-α2b (PEG-IFN) versus observation in resected stage III melanoma: Long-term results at 7.6-years follow-up.
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2011
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Surgical OncologyVersus ObservationMedicineEortc 18991MelanomaImmunologyPhase Iii TrialLargest Adjuvant TrialStage Iii MelanomaDermatologyCancer TreatmentImmunotherapyOncologyRadiation OncologyCancer ResearchMolecular OncologyLong-term Results
8506b Background: EORTC 18991 is the largest adjuvant trial ever conducted in stage III melanoma. It assessed the efficacy and toxicity of long-term PEG-IFN vs Observation (Obs.). Methods: PEG-IFN (Induction at 6µg/Kg/wk, sc, 8 weeks; followed by Maintenance at 3µg/Kg/wk, sc) for a total treatment duration of up to 5 years was compared to Obs. in 1256 patients (pts) with stage III melanoma (anyTN1-2M0 without in-transit metastases). Randomization was stratified for nodal involvement N1 (microscopic) vs N2 (palpable nodes), # of nodes, Breslow and ulceration of primary, sex and center. Distant metastasis-free survival (DMFS) was the primary endpoint. Relapse-free survival (RFS) was the pre-specified regulatory primary endpoint. Overall survival (OS) was the secondary endpoint. Intent-to-treat analysis was performed Results: Median follow-up was 7.6 yrs is shown in the table. Conclusions: Long-term PEG-IFN therapy in stage III melanoma had a significant and sustained impact on RFS, but not on DMFS and OS. Pts with only microscopic nodal involvement (sentinel node positive) seemed to have a greater benefit of PEG-IFN in terms of RFS, and marginally regarding DMFS and OS. In the smaller subgroup of pts with sentinel node positive and with ulcerated melanoma, the benefit seemed to be the most striking and consistent regarding all endpoints, and was maintained at long term follow-up. These effects have been observed in 2 consecutive EORTC trials (18952 and 18991) involving 2,644 pts. RFS DMFS OS All pts (N=1,256) Obs. PEG-IFN Obs. PEG-IFN Obs. PEG-IFN Nb. events 406 384 375 370 336 332 7-year rates 35% 39% 40% 42% 46% 48% Median (yrs) 2.2 3.0 3.2 3.9 5.6 6.2 HR (95%CI) 0.87 (0.76-1.00) 0.93 (0.81-1.07) 0.96 (0.82-1.11) P value 0.05 0.33 0.57 N2 pts (N=713) HR (99%CI) 0.89 (0.71-1.13) 0.96 (0.76-1.22) 1.00 (0.78-1.29) P value 0.21 0.66 0.97 N1 pts (N=543) HR (99%CI) 0.82 (0.61-1.10) 0.86 (0.63-1.17) 0.86 (0.62-1.21) P value 0.08 0.22 0.26 N1 pts & ulc. (N=186) HR (99%CI) 0.72 (0.46-1.13) 0.65 (0.41-1.04) 0.59 (0.35-0.97) p-value 0.06 0.02 0.006 Abbreviations: HR, hazard ratio; CI, confidence interval; N1, microscopic (sentinel node positive); N2, palpable nodes; ulc., ulcerated melanoma.