Ulceration and stage are predictive of interferon efficacy in melanoma: Results of the phase III adjuvant trials EORTC 18952 and EORTC 18991
Adjuvant interferon has modest activity in melanoma patients at high risk for relapse. Patient selection is important; stage and ulceration of the primary tumour are key prognostic factors. Methods: In this post hoc meta-analysis of European Organisation for Research and Treatment of Cancer (EORTC) trials 18952 (intermediate doses of interferon α-2b [IFN] versus observation in stage IIb-III patients) and 18991 (pegylated [PEG]-IFN versus observation in stage III patients), the predictive value of ulceration on the efficacy of IFN/PEG-IFN with regard to relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) was assessed in the overall population and in subgroups stratified by stage (IIb and III-N1 [microscopic nodal disease] and III-N2 [macroscopic nodal disease]). Findings: In the overall population, the comparison of IFN/PEG-IFN versus observation for RFS, DMFS and OS yielded estimated hazard ratios (HR) of 0.85 (p = 0.004), 0.89 (p = 0.04) and 0.94 (p = 0.36), respectively. The impact of treatment was greater in the ulceration group (n = 849) compared with the non-ulceration group (n = 1336) for RFS (test for interaction: p = 0.02), DMFS (p < 0.001) and OS (p < 0.001). The greatest risk reductions were observed in patients with ulceration and stage IIb/III-N1, with estimated HR for RFS, DMFS, and OS of 0.69 (p = 0.003), 0.59 (p < 0.0001) and 0.58 (p < 0.0001), respectively. The efficacy of IFN/PEG-IFN was lower in stage III-N2 patients with ulceration and uniformly absent in patients without ulceration. There was consistency between the data of both trials. Interpretation: This meta-analysis of the EORTC 18952 and 18991 trials indicated that both tumour stage and ulceration were predictive factors for the efficacy of adjuvant IFN/PEG-IFN therapy.
|Keywords||Adjuvant Interferon Efficacy, Melanoma, Phase III Trials, Predictive Factors, Stage, Ulceration|
|Persistent URL||dx.doi.org/10.1016/j.ejca.2011.09.028, hdl.handle.net/1765/61916|
|Journal||European Journal of Cancer|
Eggermont, A.M.M, Suciu, S, Testori, A, Kruit, W.H.J, Marsden, J, Punt, C.J.A, … Spatz, A. (2012). Ulceration and stage are predictive of interferon efficacy in melanoma: Results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. European Journal of Cancer, 48(2), 218–225. doi:10.1016/j.ejca.2011.09.028