Intermittent intensified high-dose intravenous interferon alpha 2b (IFNa2b) for adjuvant treatment of stage III malignant melanoma: Pooled analysis of two randomized phase III trials (NCT00226408 and ISRCTN75125874) with 980 patients.

Abstract

e20028 Background: Adjuvant high-dose interferon (HDI) treatment of patients (pts) with malignant melanoma (MM) consists of 4 weeks intravenous (IV) induction with 20 MU/m² interferon (IFN) alpha 2b followed by 11 months of 10 Mio IU/m² IFN subcutaneously (sc). It is unclear whether both parts of the regimen are mandatory for the efficacy of HDI treatment. The adjuvant phase III trials DeCOG MM-ADJ-5 and the Italian Melanoma Intergroup (IMI) trial evaluated intermittent IV HDI (iHDI) regimens as compared to standard HDI. In both trials, the experimental arm consisted of iHDI for 3 or 4 cycles, respectively. To gain more insight into the role of iHDI in the adjuvant setting we performed a pooled analysis of both trials. Methods: Based on the intent-to-treat populations, the German DeCOG trial contributed data on 627 MM pts. with stage III (AJCC 2002) resected intransit or lymph node metastasis. From the Italian IMI trial 330 pts. with stage III regional lymph node metastasis excluding intransit metastasis were evaluable. We performed a combined analysis with respect to relapse free survival (RFS) and overall survival (OS), and toxicity using Cox regression models. Results: Median follow-up was 4.6 years in the DeCOG trial and 7.2 years in the IMI trial. There were 320 relapses in the DeCOG trial (51%) and 179 relapses in the IMI trial (54%) resulting in a combined hazard ratio (HR) for RFS of 1.11 (95% CI 0.93; 1.33) comparing iHDI vs.conventional HDI. OS was similar for iHDI vs. conventional HDI (HR 1.04; 95% CI 0.84; 1.29). There was no significant heterogeneity comparing different substages (IIIA vs. IIIB vs. IIIC) or ulcerated versus non-ulcerated primary tumors. In both studies more patients discontinued treatment due to toxicity or impairment of quality of life with conventional HDI as compared to iHDI (DeCOG: 31.0% vs. 16.7%; IMI: 31.2% vs. 23.8%). Conclusions: The pooled analysis of the two pulsed adjuvant HDI treatments showed no significant differences for RFS or OS as compared to conventional HDI. There is a favorable safety profile and less overall toxicity in the pulsed regimens.