No Difference in Overall Survival, Poorer Relapse-Free Survival With Adjuvant Intermittent vs High-Dose Interferon Alfa-2b in Stage III Melanoma
The final analysis of a European Dermatologic Cooperative Oncology Group phase III trial, reported in the Journal of Clinical Oncology by Mohr et al, showed that adjuvant intermittent vs standard high-dose intravenous interferon alfa-2b was associated with no difference in overall survival but poorer relapse-free survival in stage III melanoma. Discontinuation of treatment was less common with the intermittent regimen.
Study Details
In the open-label trial, 627 evaluable patients from 23 German, 1 Austrian, 1 Greek, and 1 Swiss center were randomly assigned between September 2003 and July 2009 to receive three courses of intravenous interferon-alfa-2b 20 MIU/m2 5 days a week for 4 weeks then repeated every 4 months (n = 311) or a standard high-dose interferon-alfa-2b regimen (n = 316). Standard treatment consisted of intravenous interferon-alfa-2b 20 MIU/m2 from days 1 to 5, days 8 to 12, days 15 to 19, and days 22 to 26; starting from day 29 in week 5, patients received interferon-alfa-2b 10 MIU/m2 subcutaneously 3 times per week for 48 weeks.
The primary endpoint was distant metastasis–free survival. Secondary endpoints included relapse-free survival, overall survival, and quality of life measured by the EORTC Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30).
No Overall Survival Difference
Median follow-up was 55.3 months in the intermittent group and 55.4 months in the standard group. Estimated 5-year rates for the intermittent vs standard groups were 49.2% vs 53.1% for distant metastasis–free survival, 62.9% vs 64.1% for overall survival, and 42.6% vs 48.5% for relapse-free survival.
On multivariate analysis, the hazard ratios were 1.21 (P = .12) for distant metastasis-free survival, 1.01 (P = .85) for overall survival, and 1.27 (P = .03) for relapse-free survival.
Quality of Life and Toxicity
Global quality-of-life score decreased similarly in both groups during the first 4 weeks of high-dose treatment. Four weeks later, the score fully recovered in the intermittent group and then exceeded baseline during weeks 8 to 15 off therapy; scores decreased again during the following intravenous cycles, and then completely recovered. In the standard group, scores remained decreased during the subcutaneous phase following intravenous induction.
Discontinuation of treatment occurred in 6.8% vs 14.6% of patients due to adverse events and in an additional 8.0% vs 11.4% due to impaired quality of life. Anemia of any grade (48% vs 31%) and grade 3 or 4 fatigue (21% vs 12%) and neuropsychiatric events (5.7% vs 3.2%) were more common in the standard group; grade 3 or 4 neutropenia (39% vs 30%) was more common in the intermittent group.
The investigators concluded: “Although the safety and [quality-of-life] profiles for the intermittent regimen were favorable, no significant difference was observed for survival while the [hazard ratio] for relapse with [intermittent high-dose interferon-alfa-2b] was increased. Therefore, an [intermittent high-dose interferon-alfa-2b] regimen, as tested here, cannot be recommended as adjuvant treatment for high-risk melanoma.”
Peter Mohr, MD, of Elbe-Klinikum Buxtehude, Germany, is the corresponding author for the Journal of Clinical Oncology article.
For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
