Long-Term Results of Adjuvant Endocrine Therapy in Premenopausal Breast Cancer
In an analysis of long-term outcomes in the SOFT and TEXT trials reported at the 2018 ASCO Annual Meeting and in The New England Journal of Medicine, Francis et al found that the addition of ovarian suppression to adjuvant tamoxifen significantly improved 8-year rates of disease-free and overall survival vs tamoxifen alone among premenopausal women with breast cancer; risk of recurrence was further reduced with exemestane plus ovarian suppression.
Initial reports showed that 5-year rates of recurrence were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression vs tamoxifen plus ovarian suppression, with the addition of ovarian suppression to tamoxifen not significantly improving recurrence risk vs tamoxifen alone.
Study Details
The current analysis presents results of a prespecified updated analysis of SOFT and combined analysis of SOFT and TEXT after median follow-up of 8 and 9 years in the trials, respectively.
In the trials, women were randomized to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT, and to tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified by receipt of chemotherapy.
Long-Term Outcomes
In SOFT, 8-year disease-free survival rates were 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (hazard ratio [HR] = 0.76, P = .009) for tamoxifen plus ovarian suppression vs tamoxifen alone; HR = 0.65, 95% confidence interval [CI] = 0.53–0.81 for exemestane plus ovarian suppression vs tamoxifen alone). Overall survival at 8 years was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression (HR = 0.67, P = .01, vs tamoxifen alone), and 92.1% with exemestane plus ovarian suppression (HR = 0.85, 95% CI = 0.62–1.15, vs tamoxifen alone); the respective survival rates among women who remained premenopausal after chemotherapy were 85.1%, 89.4%, and 87.2%.
In the combined analysis of the two trials including patients who were assigned ovarian suppression, 8-year disease-free survival rates were 86.8% with exemestane plus ovarian suppression vs 82.8% with tamoxifen plus ovarian suppression (HR = 0.77, P < .001) and 8-year overall survival rates were 93.4% vs 93.3% (HR = 0.98, P = .84). The majority of patients in the two trials had HER2-negative disease. Among these women who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression by an absolute 7.0% in SOFT and 5.0% in TEXT.
Adverse events of grade ≥ 3 occurred in 24.6% of the tamoxifen group, 31.0% of the tamoxifen plus ovarian suppression group, and 32.3% of the exemestane plus ovarian suppression group.
The investigators concluded, “Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group.”
The study was funded by Pfizer and others.
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®.
