Background

First results of the TEXT and SOFT international phase III trials were practice-changing, indicating that: i) 5y adjuvant exemestane+ovarian function suppression (E+OFS) reduces recurrence risk relative to tamoxifen(T)+OFS or to T alone, ii) T+OFS reduces recurrence risk vs T in women who are at sufficient risk to warrant chemotherapy (CT) and remain premenopausal afterwards, and iii) T alone remains appropriate for some premenopausal women. However, median follow-up (FU) was only 5.5y and <5% pts had died. FU is immature given the long natural history of HR+ disease and EBCTCG overviews showing overall survival (OS) improvements for T vs no-T emerged during 5-15y. It is crucial to establish if changing standard adjuvant endocrine therapy from T improves survival and if there are associated late toxicities.

Trial Design and Aims

Premenopausal women had invasive early breast cancer (BC) assessed as ≥10% ER and/or PgR.

SOFT was designed to determine the value of adding OFS to T, and the role of E+OFS in two cohorts: women who remained premenopausal after completion of neo/adjuvant CT, and women for whom adjuvant T alone was considered suitable treatment. SOFT compares 5y of T to T+OFS or E+OFS. OFS was GnRH analog triptorelin x5y, oophorectomy or ovarian irradiation. Median age was 43y; 35% had N+ disease. 53% enrolled after prior neo/adjuvant CT.

TEXT was designed to determine the role of adjuvant E in premenopausal women receiving OFS from the start of adjuvant therapy, comparing 5y of E+OFS vs T+OFS. Patients enrolled at start of all adjuvant therapy; 60% had CT concurrent with triptorelin after entry. Median age was 43y; 48% had N+ disease.

Secondary objectives include effects on OS, late side effects of early menopause and late toxicities.

Accruals

TEXT: 2672 women, Nov03-Mar11

SOFT: 3066 women, Dec03-Jan11

Statistical Methods

The primary endpoint, invasive disease-free survival, is time from randomization to invasive local, regional, or distant relapse, contralateral BC, second non-BC malignancy, or death. Secondary endpoints are BC-free interval, distant recurrence-free interval and OS. Primary results were reported in 2014, after ∼5.5y median FU; 30% pts were still on 5y treatment and >90% continued in FU.

Long-term FU

Updated results are planned for FU through Dec16, with ∼8y median FU. Pts finished 5y treatment by Apr16. Yearly visits continue; data collection includes weight, performance status, menstrual status, pregnancy attempts, GYN procedures, late AEs (cardiovascular, bone fracture), extended adjuvant therapy, invasive recurrence at first and subsequent sites, second non-BC malignancy, in situ cancers, OS.

FU through 2020 is planned, for min and median FU of 10 and 12y, roughly doubling the numbers of endpoints events since the first report. This will be critical to determine whether short-term treatment benefits persist for late recurrence, improve power to detect treatment effects on distant recurrence and OS endpoints with lower event rates occurring later in FU, and define associated late toxicities and side effects of early menopause. A consortium to fund long-term FU is being pursued.

Citation Format: Francis PA, Fleming GF, Regan MM, Pagani O, Walley BA, Price KN, Coates AS, Goldhirsch A, Gelber R. Long-term follow-up of TEXT and SOFT trials of adjuvant endocrine therapies for premenopausal women with HR+ early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-02-03.