Quality-of-life-adjusted survival analysis of high-dose adjuvant interferon alpha-2b for high-risk melanoma patients using intergroup clinical trial data.

Abstract

High-dose adjuvant interferon alpha-2b (IFN alpha 2b) for high-risk melanoma is a 1-year regimen that improves relapse-free and overall survival but has significant toxicity. A quality-of-life--adjusted survival (QAS) analysis analysis of two cooperative group phase III trials, E1684 and E1690/S9111/C9190, was performed, incorporating patient values (utilities) for the toxicity of IFN alpha 2b treatment and melanoma recurrence. Quality-Adjusted Time Without Symptoms or Toxicity methodology was used with melanoma patient utilities and trial data to estimate the effect of IFN alpha 2b on QAS. The increase or decrease in QAS that patients could expect from treatment was estimated based on their utilities. Eleven utility predictor questions were tested to identify patients with utilities that result in decreased QAS. Using E1684 data, IFN alpha 2b would result in an increase in QAS for all sets of patient utilities. This benefit was significant (P <.05) for 16% of patients. Using E1690/S9111/C9190 data, 77% of patients would experience a benefit in QAS from IFN alpha 2b and 23% would experience a decrease in QAS; neither of these effects was statistically significant. Using utility predictors and the E1690/S9111/C9190 analysis, a decision rule was formulated that helps identify patients in whom IFN alpha 2b may detract from QAS. Most patients experienced improvement in QAS in both trials, but this benefit was statistically significant in only 16% of patients in E1684. Change in QAS depends more on the utility for IFN alpha 2b toxicity than on the utility for melanoma recurrence. Cancer patients probably have higher utilities for IFN alpha 2b toxicity than members of the general population and will tend to favor IFN alpha 2b treatment as a result.