After two trials and more than 12 years of follow-up, researchers concluded that ovarian function suppression (OFS) plus endocrine therapy improves both disease-free (DFS) and overall survival (OS) for patients with premenopausal breast cancer compared to endocrine therapy alone and that exemestane has an advantage over tamoxifen for some patients. The authors reported their findings in two articles in the Journal of Clinical Oncology.
For the SOFT trial, researchers randomly assigned premenopausal patients with hormone receptor–positive breast cancer to five years of adjuvant tamoxifen, tamoxifen plus OFS, or exemestane plus OFS. After a median follow-up of 12 years, DFS was 71.9% with tamoxifen, 76.1% with tamoxifen plus OFS, and 79.0% with exemestane plus OFS; OS was 86.8% with tamoxifen, 89.0% with tamoxifen plus OFS, and 89.4% with exemestane plus OFS. Among those who received prior chemotherapy for HER2-negative tumors, OS was 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS, and 84.4% with exemestane plus OFS.
The researchers combined SOFT’s results with those from the TEXT trial to compare outcomes in 4,690 premenopausal patients with estrogen or progesterone receptor–positive early breast cancer randomly assigned to five years of exemestane plus OFS versus tamoxifen plus OFS. After a median follow-up of 13 years, the 12-year DFS and distant recurrence-free interval were significantly improved (4.6% and 1.8%, respectively) for patients assigned exemestane plus OFS over tamoxifen plus OFS. Among patients with HER2-negative tumors, the absolute improvement in 12-year overall survival with exemestane plus OFS was 2.0% and 3.3% in those who received chemotherapy. Overall survival benefit was clinically significant in high-risk patients (e.g., younger than 35 years, tumors larger than 2 cm, grade 3 tumors).
“After 12 years, there remains a benefit from including OFS in adjuvant endocrine therapy, with an absolute improvement in OS more apparent with higher baseline risk of recurrence,” the SOFT researchers concluded.
“These sustained reductions of the risk of recurrence with adjuvant exemestane plus OFS, compared with tamoxifen plus OFS, provide guidance for selecting patients for whom exemestane should be preferred over tamoxifen in the setting of OFS,” the authors of the combined analysis concluded.