Artigo

Final outcomes of the SOFT and TEXT phase III trials in premenopausal hormonereceptor-positive early breast cancer

Autor(es): P.A. Francis1,2,3, O. Pagani4,5,6, G.F. Fleming7 , B.A. Walley8 , M. Colleoni9 , G. Rubovszky10 , C. Tondini11, E.M. Ciruelos12,13, H.L. Gomez14, H.R. Bonnefoi15,16, H.J. Burstein17,18,19, C. Chini20, F. Puglisi21,22, S. Spazzapan23, A. Bernardo24, M.A. Climent13,25, M. Bellet13,26,27, T. Ruhstaller6,28, B. Bermejo13,29, S.K.L. Chia30,31,32, S. Martino33 , C.E. Geyer, Jr.34,35 , M.P. Goetz19,36 , J.N. Ingle19,36 , V. Stearns37 , N.E. Davidson38,39 , F. Le Du40 , B. Müller41 , R.E. Coleman42,43,44 , S. Loibl45,46 , E.P. Winer47 , B. Ruepp48 , S. Loi3,49,50, I. Láng51 , A.S. Coates3,52 , R.D. Gelber18,53,54,55,56 , A. Goldhirsch†18,57 & M.M. Regan18,53,54 for the International Breast Cancer Study Group* and the SOFT and TEXT Investigators**

Background: The SOFT trial found adding ovarian function suppression (OFS) to tamoxifen (T) reduced breast cancer recurrence, and exemestane (E)+OFS further reduced recurrence. SOFT and TEXT combined analysis showed a significant reduction in distant recurrence with E+OFS versus T+OFS. We now report final 15-year outcomes. Patients and methods: Premenopausal women with hormone receptor-positive early breast cancer were enrolled, with 3047 in SOFT and 2660 in TEXT intention-to-treat populations. SOFT randomized to 5 years of T versus T+OFS versus E+OFS. TEXT randomized to 5 years of T+OFS versus E+OFS. Chemotherapy was optional, prior to SOFT entry with
subsequent premenopausal oestradiol, or concurrent with OFS in TEXT. Endpoints included disease-free survival, breast cancer-free interval (BCFI), distant recurrence-free interval (DRFI) and overall survival. 15-year Kaplan-Meier estimates, hazard ratios (HR) and 95% confidence intervals (CI) are reported.
Results: In SOFT, escalating endocrine therapy (ET) continued to reduce recurrence with 15-year BCFI 78.6% for E+OFS, 75.7% for T+OFS and 72.1% for T; T+OFS versus T, HR 0.82 (CI 0.69-0.98) P=0.03. In the SOFT no-chemotherapy cohort, OFS reduced breast cancer events at 15 years, while DRFI and overall survival remained high regardless of ET assignment. After prior chemotherapy for HER2-negative tumours (n=1257), SOFT 15-year overall survival was 81.0% with E+OFS versus 77.1% with T+OFS versus 76.8% with T. In women under age 35 with HER2-negative tumours (n=241), 15-year overall survival was 82.5% with E+OFS, 77.9% with T+OFS and 68.1% with T. In combined SOFT and TEXT analysis, among those with HER2-negative tumours (n=4035), E+OFS versus T+OFS
reduced distant recurrence HR 0.75 (CI 0.63-0.90), with a smaller reduction in deaths HR 0.89 (CI 0.74-1.06), with absolute survival benefits largest with high-risk features, particularly young age or high-grade tumours.
Conclusion: Meaningful overall survival benefit in hormone receptor-positive, HER2- negative breast cancer from adjuvant exemestane and/or OFS compared with tamoxifen alone is limited to high-risk premenopausal subgroups. Tamoxifen-based ET may not result in optimal outcomes in premenopausal high-grade HER2-negative tumours.