Background The updated combined SOFT+TEXT analysis, after 9 years median follow-up (MFU), revealed that adjuvant E+OFS vs T+OFS significantly improved disease-free survival (DFS) and distant recurrence-free interval (DRFI) but not overall survival (OS) in premenopausal women with HR+ early BC (Francis et al NEJM 2018). Given the high rate of OS in both arms and the long-term risk of relapse in HR+ BC, continued follow-up is key to assessing treatment benefit. We report a planned update analysis including OS with database lock of May 2021, after 13 years MFU.. Methods TEXT and SOFT enrolled premenopausal women with HR+ early BC from November 2003 to April 2011 (2660 in TEXT, 3047 in SOFT intention-to-treat (ITT) populations). TEXT randomized women within 12 weeks of surgery to 5 years E+OFS vs T+OFS; chemotherapy (CT) was optional and concurrent with OFS. SOFT randomized women to 5 years 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. For the combined analysis of E+OFS vs T+OFS, the primary endpoint was DFS defined as invasive local, regional, distant recurrence, contralateral BC, second malignancy, death. Secondary endpoints included invasive breast cancer-free interval (BCFI), DRFI and OS.. Results: At database lock there were 953 DFS events and 473 deaths among 4690 pts assigned to T+OFS or E+OFS. In the ITT population, DFS, BCFI and DRFI outcomes for pts assigned E+OFS (n=2346) continued to be significantly improved over T+OFS (n=2344). 12-yr DFS was 80.5% vs. 75.9% (4.6% absolute improvement; HR 0.79 95% CI 0.70-0.90), 12-yr BCFI was improved by 4.1% and 12-yr DRFI by 1.8%. At 12 years OS was excellent in both groups, 90.1% in pts assigned E+OFS vs 89.1% in pts assigned T+OFS (HR 0.93; 95% CI, 0.78-1.11). There was heterogeneity of relative treatment effect according to HER2 status. When enrollment commenced, anti-HER2 adjuvant therapy was not standard; 53% of 583 pts with HER2+ tumors received HER2-targeted therapy. Below are Kaplan-Meier 12-yr estimates for patients with HER2 negative tumors by trial and chemotherapy stratum and for those with high-grade tumours, as an example of high-risk feature (Table). There is an emerging OS benefit for E+OFS vs T+OFS in pts with HER2 negative tumors who received chemotherapy in both trials.In pts with HER2-negative tumors, clinically-relevant outcome benefits were also seen in other high-risk subgroups: 12-yr DFS and OS were improved by 7.4% and 2.7%, respectively, in pts with pN1a disease, and by 10.6% and 4.5%, respectively, in those with tumors >2cm.

Conclusions After 13 years MFU, adjuvant E+OFS, as compared with T+OFS, shows a sustained reduction in the risk of recurrence, more consistent in HER2 negative patients and in those with high-risk disease features, e.g., indication for adjuvant chemotherapy and G3 tumors. Oncologists may use this information to discuss potential benefits of E+OFS with individual patients. Follow-up continues for 5 additional years.

Chemotherapy HER2-negative 
SOFT 
 T+OFS (n=424) E+OFS (n=411) Absolute difference 
12-yr DFS 67.4% 74.1% 6.7% 
12-yr OS 81.1% 84.4% 3.3% 
TEXT 
 T+OFS (n=656) E+OFS (n=661) Absolute difference 
12-yr DFS 71.0% 78.4% 7.4% 
12-yr OS 83.5% 86.8% 3.3% 
No chemotherapy HER2-negative 
SOFT 
 T+OFS (n=445) E+OFS (n=447) Absolute difference 
12-yr DFS 82.9% 88.2% 5.3% 
12-yr OS 96.1% 96.9% 0.9% 
TEXT    
 T+OFS (n=499) E+OFS (n=492) Absolute difference 
12-yr DFS 80.2% 86.7% 6.5% 
12-yr OS 95.9% 96.2% 0.2% 
G3 HER2-negative    
 T+OFS (n=423) E+OFS (n=405) Absolute difference 
12-yr DFS 62.7% 73.0% 10.3% 
12-yr OS 78.1% 83.6% 5.5% 
Chemotherapy HER2-negative 
SOFT 
 T+OFS (n=424) E+OFS (n=411) Absolute difference 
12-yr DFS 67.4% 74.1% 6.7% 
12-yr OS 81.1% 84.4% 3.3% 
TEXT 
 T+OFS (n=656) E+OFS (n=661) Absolute difference 
12-yr DFS 71.0% 78.4% 7.4% 
12-yr OS 83.5% 86.8% 3.3% 
No chemotherapy HER2-negative 
SOFT 
 T+OFS (n=445) E+OFS (n=447) Absolute difference 
12-yr DFS 82.9% 88.2% 5.3% 
12-yr OS 96.1% 96.9% 0.9% 
TEXT    
 T+OFS (n=499) E+OFS (n=492) Absolute difference 
12-yr DFS 80.2% 86.7% 6.5% 
12-yr OS 95.9% 96.2% 0.2% 
G3 HER2-negative    
 T+OFS (n=423) E+OFS (n=405) Absolute difference 
12-yr DFS 62.7% 73.0% 10.3% 
12-yr OS 78.1% 83.6% 5.5% 

Citation Format: Meredith M Regan, Barbara A Walley, Gini F Fleming, Prudence A Francis, Marco A Colleoni, István Láng, Henry L Gómez, Carlo A Tondini, Harold J Burstein, Matthew P Goetz, Eva M Ciruelos, Vered Stearns, Hervé R Bonnefoi, Silvana Martino, Charles E Geyer, Jr, Claudio Chini, Alessandro M Minisini, Simon Spazzapan, Thomas Ruhstaller, Eric P Winer, Barbara Ruepp, Sherene Loi, Alan S Coates, Aron Goldhirsch, Richard D Gelber, Olivia Pagani. Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): update of the combined TEXT and SOFT trials [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS2-05.