Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCICCTG MA.17

Background: MA. 17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease- free survival ( DFS) for letrozole [ hazard ratio ( HR) 0.57, P = 0.00008]. The trial was unblinded and placebo patients were offered letrozole. Patients and methods: An intent- to- treat analysis of all outcomes, before and after unblinding, on the basis of the original randomization was carried out. Results: In all, 5187 patients were randomly allocated to the study at baseline and, at unblinding, 1579 ( 66%) of 2383 placebo patients accepted letrozole. At median follow- up of 64 months ( range 16 - 95), 399 recurrences or contralateral breast cancers ( CLBCs) ( 164 letrozole and 235 placebo) occurred. Four- year DFS was 94.3% ( letrozole) and 91.4% ( placebo) [ HR 0.68, 95% confidence interval ( CI) 0.55 - 0.83, P = 0.0001] and showed superiority for letrozole in both node- positive and - negative patients. Corresponding 4- year distant DFS was 96.3% and 94.9% ( HR 0.80, 95% CI 0.62 - 1.03, P = 0.082). Four- year overall survival was 95.1% for both groups. The annual rate of CLBC was 0.28% for letrozole and 0.46% for placebo patients ( HR 0.61, 95% CI 0.39 - 0.97, P = 0.033). Conclusions: Patients originally randomly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC, despite 66% of placebo patients taking letrozole after unblinding.