15-year outcomes for women with premenopausal hormone receptor-positive early breast cancer (BC) in the SOFT and TEXT trials assessing benefits from adjuvant exemestane (E) + ovarian function suppression (OFS) or tamoxifen (T)+OFS.
Prudence A. Francis, Gini F. Fleming, Olivia Pagani, Barbara Walley, Sherene Loi, Marco Colleoni, Meredith M. Regan, on behalf of SOFT and TEXT Investigators, IBCSG, BIG and North American BC Groups
Abstract
505 Background: Long-term follow-up of the SOFT and TEXT randomized trials has shown persistent reduction of recurrence from inclusion of OFS in adjuvant endocrine therapy, and clinically meaningful improvement in overall survival (OS) among patients at higher baseline risk of recurrence. We report a final update after a median follow-up of 15y in SOFT and 16.6y in TEXT. Methods: SOFT and TEXT enrolled premenopausal women with HR+ early BC from November 2003 to April 2011 (2660 in TEXT, 3047 in SOFT intention-to-treat populations). TEXT randomized women within 12 weeks of surgery to 5y E+OFS vs T+OFS; chemotherapy (CT) was optional and concurrent with OFS. SOFT randomized women to 5y E+OFS vs T+OFS vs T alone, within 12 weeks of surgery if no CT planned, or within 8 months of completing (neo)adjuvant CT. Both trials were stratified by CT use. The primary endpoint was disease free survival (DFS) which included invasive local, regional, distant and contralateral breast events, second non-breast malignancies and deaths. Secondary endpoints included invasive breast cancer-free interval (BCFI), distant recurrence free interval (DRFI) and OS. 20y data collection was completed in Q4’2024: 80% of surviving patients had final follow-up during or subsequent to 2020, for 70% it was during 2023-2024. 15y Kaplan-Meier estimates and hazard ratios (HR) with 95% CIs are reported. Results: There were 815 DFS events and 388 deaths reported in SOFT; and 669 DFS events and 325 deaths in TEXT. In SOFT, a moderate DFS benefit of T+OFS vs T (HR 0.85; 0.72-1.00) persisted, however 1/6 DFS events were not BC related; BCFI benefit was HR 0.82 (0.69-0.98). E+OFS vs T further reduced DFS events (HR 0.73; 0.61-0.86). The 15y DFS in SOFT was 67.0% for T, 70.5% for T+OFS and 73.5% for E+OFS. There were consistent but non-significant decreased hazards of death for T+OFS vs T (HR 0.87; 0.68-1.10) and E+OFS vs T (HR 0.85; 0.67-1.08). 15y OS was 85.3%, 86.7%, 86.9% respectively. For the TEXT+SOFT combined analysis of E+OFS vs T+OFS (n=2346 vs 2344) DFS, BCFI and DRFI continued as significantly improved for E+OFS over T+OFS. 15y DFS was 74.9% vs 71.3% (HR 0.82; 0.73-0.92). 15y OS was 87.8% vs 87.0% (HR 0.94; 0.80-1.11) respectively. 15y estimates by CT use are tabulated. Conclusions: The high level 15y final results of the SOFT and TEXT confirm a role for OFS- and aromatase inhibitor-containing adjuvant endocrine therapy for premenopausal women. Analysis is ongoing. Clinical trial information: NCT00066690 (SOFT) and NCT00066703 (TEXT) . 15y (%) Events SOFT Prior CT (n=1628) SOFT no CT (n=1419) CT+noCT T / T+OFS / E+OFS T / T+OFS / E+OFS DFS 536+279 60.9 / 63.0 / 66.3 73.9 / 79.1 / 82.1 DRFI 367+56 73.5 / 73.8 / 77.6 94.7 / 94.7 / 96.8 OS 318+70 77.4 / 79.4 / 79.8 94.4 / 95.1 / 95.2 TEXT CT (n=1607) TEXT no CT (n=1053) T+OFS / E+OFS T+OFS / E+OFS DFS 456+213 68.5 / 72.1 76.8 / 81.8 DRFI 286+69 79.0 / 81.3 91.6 / 94.6 OS 266+59 82.7 / 84.3 94.1 / 94.8