Abstract OT2-2-01: SOFT and TEXT: Trials of tamoxifen and exemestane with and without ovarian function suppression for premenopausal women with hormone receptor-positive early breast cancer
Authors: L Zickl, P Francis, G Fleming, O Pagani, B Walley, KN Price, RD Gelber, MM Regan
Journal: Cancer Research (2012)

Abstract Background: The SOFT and TEXT randomized phase 3 trials address two primary questions for endocrine treatment of premenopausal women with hormone receptor-positive breast cancer. 1) In combination with ovarian function suppression (OFS), does an aromatase inhibitor (exemestane, E) improve outcome compared with tamoxifen (T)? 2) Does addition of OFS to T improve outcome compared with T alone? Trial Designs: SOFT compares 5y of T to OFS+T or OFS+E. OFS can be GnRH analog (triptorelin) × 5y, oophorectomy or ovarian irradiation. Median age was 43y (11% &amp;lt;35y); 35% had N+ disease. Prior neo/adjuvant chemotherapy (CT) given in 53%. TEXT compares 5y of OFS+T to OFS+E. Patients were enrolled prior to CT (if planned). Median age was 43y (9% &amp;lt;35y); 48% had N+ disease. Adjuvant CT was planned in 60%. Major Eligibility Criteria – Premenopausal, confirmed by estradiol levels– ER≥10% and/or PgR≥10%– Invasive early breast cancer Specific Aims: Evaluate the role of aromatase inhibitors and the addition of OFS to T in this population. Statistical Methods (amended 2011): The primary analysis will be intention-to-treat of all randomized patients. The primary endpoint, invasive disease-free survival (DFS), is defined as time from randomization to invasive local, regional, or distant relapse, contralateral breast cancer, appearance of a second non-breast malignancy, or death. DFS will be compared using a 2-sided stratified logrank test with an overall experiment-wise alpha level equal to at most 0.05. In the original protocol, anticipated 5y DFS was 67% with T alone, 74% with OFS+T, and 79.8% with OFS+E, and required a total of 396 DFS events in TEXT and 783 DFS events in SOFT to reach 80% power. Because the enrolled population had more favorable characteristics and the event rates were lower than anticipated (2%/yr vs 8%/yr), the revised analysis plan is ‘time-driven’ rather than ‘event-driven.’ The comparison of OFS+E to OFS+T across both trials (n = 4717) is planned at median follow-up (MFU) &amp;gt;5y. The estimated power to detect a 20%, 25%, or 30% reduction in the hazard with OFS+E vs OFS+T is 63%, 84%, and 95%, respectively. The comparison of OFS+T to T alone is planned at 5y MFU (SOFT, n=2045). The estimated power to detect a 20%, 25%, 30%, or 33.5% reduction in the hazard is 34%, 52%, 69%, and 80%, respectively. Accruals SOFT Target: 3000; Final: 3066 TEXT Target: 2639; Final: 2672 Enrollment 2003–2011; primary analyses expected late 2013/early 2014. Related Research Quality of Life (QL) component evaluates QL, menopausal symptoms and sexual impairment. TEXT Translational Research investigates patient and tumor features that may contribute to treatment effectiveness and side effects. TEXT-Bone investigates changes in bone mineral density and the role of serial serum markers of bone remodeling as predictors of bone side effects. Co-SOFT evaluates changes in cognitive function during the first year. SOFT-EST evaluates estrogen levels during the first 4y of GnRH analogue and whether there is a suboptimally estrogen-suppressed subgroup. North American Pharmacogenetics study investigates whether genetic variations that affect T and E metabolism influence efficacy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-2-01.