BIG 1-98: Randomized double-blind phase III study to evaluate letrozole (L) vs. tamoxifen (T) as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer

Authors: B. J. Thurlimann, A. Keshaviah, H. Mouridsen, L. Mauriac, J. F. Forbes, R. Paridaens, M. Castiglione-Gertsch, R. D. Gelber, I. Smith, A. Goldhirsch


Background: L has been shown to be active in postmenopausal women with endocrine-responsive breast cancer for whom prior treatment with anti-estrogens has failed, as first-line treatment for metastatic breast cancer, and in patients who remain disease-free after five years of T. The Primary Core Analysis (PCA) of BIG 1-98 comparing L (2.5 mg/d) vs. T (20 mg/d), both for 5 years, is planned for January 2005.

Methods: 8,028 postmenopausal women with endocrine-responsive breast cancer were randomized to A:Tx5 years, B:Lx5, C:Tx2→Lx3, D:Lx2→Tx3; 1,835 to the 2-arm option (A or B March 1998 to March 2000) and 6,193 to the 4-arm option (April 1999 to May 2003). Planned sample size was 7,935 to provide 80% power to detect a 20% reduction in the risk of recurrence/relapse at the 5% (2-sided) significance level. The PCA was planned after 647 disease-free survival (DFS) events (counting events in arms C and D only up to the treatment switch + 30 days), with 2 interim analyses at 261 and 430 events.

Results: The first presentation of the PCA will be at the St. Gallen Conference (January 2005). The ASCO presentation will focus on efficacy for key subgroups based on estrogen and progesterone receptor content of the primary tumor, prior chemotherapy, prior radiotherapy, and age. The PCA and safety results will be summarized for the ASCO presentation. The primary endpoint is DFS, which will be compared in the PCA for the two treatment groups using Cox model and stratified log-rank tests. The results presented will provide critical insight on the use of L relative to T for adjuvant hormone therapy of breast cancer.