Abstract GS4-02: 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
Authors: Pagani O , Regan MM , Fleming GF , Walley BA , Colleoni M , Láng I , Gomez HL , Tondini C , Burstein HJ , Goetz MP , Ciruelos EM , Stearns V , Debled M , Martino S , Geyer CE , Pinotti G , Coates AS , Goldhirsch A , Gelber RD , Francis PA 
Published: February 2018

Background: The combined results of TEXT and SOFT, after 5.7 years median follow-up, found adjuvant E+OFS significantly improved disease-free survival (DFS) vs T+OFS in premenopausal women with HR+ BC (Pagani et al, NEJM 2014). Follow-up was immature for overall survival (OS). We report a planned update with visit cut-off of 31Dec16 after 9 years median follow-up.

Methods: TEXT and SOFT enrolled premenopausal women with HR+ early BC from Nov 2003 to Apr 2011 (2660 TEXT, 3047 SOFT in the intention-to-treat populations). TEXT randomized women within 12wk of surgery to 5 yrs E+OFS vs T+OFS; chemotherapy (CT) was optional and concurrent with OFS. SOFT randomized women to 5 yrs E+OFS vs T+OFS vs T alone, within 12wk of surgery if no CT planned, or within 8mo of completing (neo)adjuvant CT after premenopausal status was (re-)established. OFS was by choice of 5yr GnRH agonist triptorelin, oophorectomy or ovarian irradiation. Both trials were stratified by CT use. The primary endpoint was DFS: randomization until invasive local, regional, distant recurrence or contralateral breast; invasive second malignancy; death. Secondary endpoints included invasive breast cancer-free interval (BCFI), distant recurrence-free interval (DRFI) and OS. Stratified Cox models estimated hazard ratios; Kaplan-Meier method estimated 8yr endpoint rates. NCT00066703/NCT00066690.

Results: DFS for patients assigned E+OFS (n=2346) continued to be significantly improved over T+OFS (n=2344): 8yr DFS was 86.8% vs. 82.8%. The 8yr BCFI was improved by 4.1% (89.3% vs 85.2%) and 8yr DRFI by 2.1% (91.8% vs 89.7%). There was no difference in OS in patients assigned E+OFS vs T+OFS: 93.4% vs 93.3% OS at 8yrs. For 1996 women without CT there have been 45 deaths, with 98% OS at 8yrs with both treatments.

EndpointN. EventsHazard Ratio (95% CI) E+OFS vs T+OFSDFS7200.77 (0.67-0.90); P&lt;0.001BCFI6000.74 (0.63-0.87)DRFI4330.80 (0.65-0.96)OS3200.98 (0.79-1.22)

Overall toxicity was not significantly worse with E+OFS than with T+OFS (32% vs 31% grade 3-4 targeted AEs). Hot flashes, musculoskeletal symptoms and hypertension were the most frequent targeted grade 3-4 AEs. Overall, 15% of patients stopped all protocol-assigned treatment early. Patients assigned E+OFS had increased risk of assigned oral endocrine therapy cessation (25% vs 19% for patients assigned T+OFS by 4yrs) but not of triptorelin cessation (18% vs 19% by 4yrs, respectively).

Conclusions: After 9 yrs median follow-up, adjuvant E+OFS, as compared with T+OFS, shows a sustained reduction of the risk of recurrence but did not improve overall survival. As in postmenopausal women, oncologists need to consider potential absolute benefits and properly select patients at sufficient risk for recurrence for whom E+OFS seems indicated. Follow-up continues, which will further clarify the effect of E+OFS for safety, late recurrence and overall survival.

Citation Format: Pagani O, Regan MM, Fleming GF, Walley BA, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Goetz MP, Ciruelos EM, Stearns V, Debled M, Martino S, Geyer Jr CE, Pinotti G, Coates AS, Goldhirsch A, Gelber RD, Francis PA. 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 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS4-02.