Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The combined analysis of SOFT-TEXT compared outcomes in 4,690 premenopausal women with estrogen/progesterone receptor–positive (ER/PgR+) early breast cancer randomly assigned to 5 years of exemestane + ovarian function suppression (OFS) versus tamoxifen + OFS. After a median follow-up of 9 years, exemestane + OFS significantly improved disease-free survival (DFS) and distant recurrence-free interval (DRFI), but not overall survival, compared with tamoxifen + OFS. We now report DFS, DRFI, and overall survival after a median follow-up of 13 years. In the intention-to-treat (ITT) population, the 12-year DFS (4.6% absolute improvement, hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.90; P < .001) and DRFI (1.8% absolute improvement, HR, 0.83; 95% CI, 0.70 to 0.98; P = .03), but not overall survival (90.1% v 89.1%, HR, 0.93; 95% CI, 0.78 to 1.11), continued to be significantly improved for patients assigned exemestane + OFS over tamoxifen + OFS. Among patients with human epidermal growth factor receptor 2-negative tumors (86.0% of the ITT population), the absolute improvement in 12-year overall survival with exemestane + OFS was 2.0% (HR, 0.85; 95% CI, 0.70 to 1.04) and 3.3% in those who received chemotherapy (45.9% of the ITT population). Overall survival benefit was clinically significant in high-risk patients, eg, women age < 35 years (4.0%) and those with > 2 cm (4.5%) or grade 3 tumors (5.5%). These sustained reductions of the risk of recurrence with adjuvant exemestane + OFS, compared with tamoxifen + OFS, provide guidance for selecting patients for whom exemestane should be preferred over tamoxifen in the setting of OFS.

Updates in the treatment of HR+HER2- breast cancer

“…Similarly, the 12 year update from the pivotal SOFT and TEXT trials, which randomized premenopausal women with HRþHER2-disease to adjuvant tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression, was published this year. These reports continue to show benefit in DFS from the addition of ovarian suppression, benefit in DFS from use of exemestane over tamoxifen with ovarian suppression, but no OS benefit of using exemestane instead of tamoxifen [37,38].…”

Update Breast Cancer 2023 Part 1 – Early Stage Breast Cancer

“…500 Patientinnen ist die Fallzahl eher klein für die adjuvante Situation. Die Vergleichsgruppe (SOFT/TEXT) wurde mehr als 10 Jahre vor der POSI-TIVE-Studie rekrutiert [67]. Die Behandlung hat sich in dieser Zeit jedoch verändert, sodass der Vergleich mit diesen Studien unter Umständen schwierig ist.…”

Hormone Receptor-Positive / HER2-Negative Early Breast Cancer High-Risk Population: An Algorithm for Optimization Systemic Adjuvant Treatment Based on 2022 Updates

“…Consequently, the authors suggest that OFS should be considered in selected cases in combination with exemestane (over tamoxifen plus OFS) mainly in cHR patients and should be offered for 5 years. 22,35 The ASTRRA trial demonstrated positive results in eventfree survival with 2 years of treatment with tamoxifen plus OFS. This finding suggests that adding OFS to TAM should be considered for those who remain in a premenopausal state or resume ovarian function after N/ACT and longer follow-up is needed to fully evaluate the OS benefit.…”