Ulceration as a Predictive Marker for Response to Interferon alfa-2b Adjuvant Therapy in Melanoma Patients
Kelly M McMasters1, *Charles R Scoggins1, *Merrick I Ross2, *Robert C G Martin, II1, Marshall Urist3, Michael J Edwards4
1University of Louisville, Louisville, KY;2Univ of Texas, MD Anderson Cancer Center, Houston, TX;3University of Alabama, Birmingham, Birmingham, AL;4University of Cincinnati, Cincinnati, OH
Several studies have demonstrated that adjuvant therapy of high-risk melanoma patients with interferon alfa-2b (IFN) improves disease-free survival (DFS), although the impact on overall survival (OS) is controversial. Recent data have suggested that IFN therapy may preferentially benefit patients with ulcerated primary tumors.
Post-hoc analysis was performed of a prospective multi-institutional randomized study of observation vs. adjuvant IFN therapy for melanoma. Patients were stratified by Breslow thickness, ulceration and nodal status. Kaplan-Meier analysis of disease-free survival (DFS) and overall survival (OS), univariate and multivariate analyses were performed.
A total of 1770 patients were analyzed (1311 without ulceration, 459 with ulceration) with a median f/u of 70 months. Overall, IFN treatment was not associated with significant improvement in DFS or OS in either SLN-negative or positive patients. However, among node-positive patients randomized to observation vs. IFN therapy (N=217), there was a significant improvement in DFS only among patients with ulcerated tumors. IFN therapy had no significant impact on OS regardless of ulceration status, however. On multivariate analysis, IFN treatment was a significant independent predictor of DFS among ulcerated patients (OR 0.65, p=0.0012), but not among patients without ulceration.
These data support the conclusion that ulceration is a predictive marker for response to adjuvant IFN therapy. Future studies should evaluate the differential effect of IFN on patients with ulcerated melanomas.