Impact of SERM adherence on treatment effect: International Breast Cancer Study Group Trials 13-93 and 14-93

Abstract

The degree of adherence to oral anticancer agents may influence treatment efficacy. Tamoxifen and toremifene usage data from two International Breast Cancer Study Group (IBCSG) studies were used to evaluate the impact of treatment adherence on the efficacy of these two selective estrogen receptor modulators (SERMs). Between 1993 and 1999, IBCSG Trial 13-93 randomized premenopausal women with node-positive disease to tamoxifen or no endocrine therapy and IBCSG Trial 14-93 compared tamoxifen and toremifene in postmenopausal women with node-positive disease. 690 women with estrogen-receptor positive enrolled in these two trials were alive and disease-free 4years after the start of SERM. The median follow up for this analysis was 9.0years. Using a Kaplan-Meier landmark analysis at 4years, the 609 women completing at least 4years of SERM had improved 10-year disease-free survival (DFS) (71%) compared with the 81 women taking less than 4years (64%), but these differences did not reach statistical significance [DFS hazard ratio (<4year/4+year) 1.31, 95% CI 0.86-1.98), p value=0.20]. Women who completed less than 4years of SERM treatment (12%) appeared not to have achieved the full benefit from their therapy. These results suggest that more effort should be made to educate women regarding the benefits of a full course of treatment. This is especially important in light of the results of the recently reported ATLAS and aTTom trials which suggest a benefit of 10years of tamoxifen.