Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up

摘要: Summary Background Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median Methods BIG is a randomised, phase 3, double-blind trial postmenopausal that compares 5 tamoxifen or letrozole monotherapy, sequential treatment 2 one these drugs followed by 3 other. Randomisation was done permuted blocks, stratified according to two-arm four-arm randomisation option, participating institution, chemotherapy use. Patients, investigators, data managers, medical reviewers were masked. The primary endpoint disease-free survival (events invasive relapse, second primaries [contralateral non-breast], death without previous event). Secondary endpoints overall survival, distant recurrence-free interval (DRFI), cancer-free (BCFI). monotherapy comparison included patients randomly assigned years. In 2005, after significant benefit reported as compared tamoxifen, protocol amendment facilitated crossover who still receiving alone; Cox models Kaplan-Meier estimates inverse probability censoring weighting (IPCW) are used account selective (n=619) arm. Comparison treatments enrolled years, Treatment has ended all detailed safety results adverse events occurred during been elsewhere. Follow-up continuing those option. registered clinicaltrials.gov NCT00004205. Findings 8010 trial, follow-up (range 0–12·4). 2459 2463 option 1546 1548 1540 At 8·7 from 0–12·4), significantly better than whether IPCW intention-to-treat analysis (IPCW HR 0·82 [95% CI 0·74–0·92], 0·79 [0·69–0·90], DRFI [0·68–0·92], BCFI 0·80 [0·70–0·92]; 0·86 [0·78–0·96], 0·87 [0·77–0·999], [0·74–0·998], [0·76–0·98]). 8·0 0–11·2) groups there no statistically differences any four either sequence. 8-year (each SE ≤1·1%) 78·6%, 77·8%, 77·3% survival; 87·5%, 87·7%, 85·9% 89·9%, 88·7%, 88·1% DRFI; 86·1%, 85·3%, 84·3% BCFI. Interpretation For endocrine-responsive cancer, reduction mortality obtained when montherapy. Sequential involving do not improve outcome but might be useful strategies considering individual patient's tolerability. Funding Novartis, United States National Cancer Institute, Study Group.