Intermittent high-dose intravenous interferon alpha 2b (IFNa2b) for adjuvant treatment of stage III malignant melanoma: An interim analysis of a randomized phase III study (NCT00226408)

Abstract

9040 Background: Adjuvant high-dose interferon (HDI) treatment of patients with malignant melanoma (MM) usually consists of an initial intravenous (iv) application of 20 Mio IU/m² IFNa2b followed by 11 months of 10 Mio IU/m² subcutaneously (sc). Up to now it is unclear whether both components are necessary for the efficacy of HDI treatment in high-risk MM patients. The adjuvant phase III DeCOG MM-ADJ-5 trial evaluates efficacy, safety, and tolerability of a pulsed high-dose intravenous IFNa2b regimen. Methods: Patients with stage III (AJCC 2002) resected malignant melanoma were randomly assigned to receive either 3 courses of IFNa2b 20 Mio IU/m² iv on 5 days a week for 4 weeks repeated every 4 months (Arm B) or the standard HDI regimen consisting of one 4 week iv course followed by 11 month of 10 MU/m² IFN a2b sc 3 times a week (Arm A). Distant metastasis free survival (DMFS) was chosen as primary endpoint for efficacy analysis. A planned interim analysis was performed after 33% of the estimated rate of distant metastasis events had been reached. With a planned recruitment of 600 patients and an estimated event rate of 50% during follow-up, there were 380 patients evaluable, when a total of 101 distant metastasis events had been reported. Results: Out of 380 patients who were evaluable, 3 patients had to be excluded from intent-to-treat analysis because of substancial protocol deviations. The remaining 377 patients were well balanced between both arms according to sex, age, and stage (IIIa: 27.0% vs 29.2%; IIIb: 43.4% vs. 45.3%; IIIc: 29.7% vs. 25.5%) Distant metastasis occurred in 48 (Arm A; 25.9 %) vs. 53 (Arm B; 27.6 %) patients without statistical difference (p=0.73). The DMFS interval was not significantly different between both arms (p=0.45; log rank test). Termination of treatment due to adverse events or impairment of patients quality of life occurred significantly more often in arm A than in arm B. (20.5% vs. 11.5%; p=0.01) Conclusions: A planned interim analysis of pulsed adjuvant HDI treatment showed no significant efficacy differences as compared to conventional HDI. There is a clear trend for a favourable safety profile and improved health related quality of life measures in the pulsed regimen. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough Schering-Plough Schering-Plough