Anastozole (A) is superior to tamoxifen (T) in treatment of postmenopausal (PM) women with early breast cancer (EBC) - First results of the ATAC (Arimidex, tamoxifen, alone or in combination) trial (on behalf of the ATAC Trialists' Group)

Abstract

ATAC, a randomized, double-blind trial compared T (20 mg) with anastrozole (A, 1 mg) (‘Arimidex’) alone, and the combination of A plus T (C), as adjuvant endocrine treatment (AET) for PM patients (pts) with EBC. It included pts with operable invasive breast cancer (BC) who had completed primary therapy and were eligible to receive AET. Main endpoints were disease-free survival (DFS) and tolerability. Other endpoints included time to recurrence (TTR: censoring non-BC deaths before recurrence) and the incidence of contralateral (CL) BC. 9366 pts were recruited (N=3125, 3116 and 3125 for A, T and C, respectively). Median duration of therapy was 30.7 months and median follow-up was 33.3 months. Total event numbers were 317, 379 and 383 for A, T and C, respectively. 84% of pts were known to be oestrogen receptor positive (ER+) and/or progesterone receptor positive (PR+). DFS was significantly improved in the overall population (pop) for A vs T (HR=0.81, 95% CI [0.71–0.96], p=0.013). A showed improved TTR compared with T (HR=0.79, [0.67–0.94], p=0.008), which improved even further in the ER+ and/or PR+ subgroup (HR=0.73, [0.59–0.90], p=0.003). An initial exploratory subgroup analysis suggested a potential interaction between A and T for prior chemotherapy use compared with no previous chemotherapy. Possible explanations for this observation, including chance, are being investigated. Longer follow-up is required before any meaningful conclusions can be made. The incidences of hot flushes, thromboembolic events, ischaemic cerebrovascular events, vaginal bleeding/discharge and endometrial cancer were significantly reduced with A compared with T (p<0.03 for all). Musculoskeletal disorders and fractures were significantly reduced in patients receiving T compared with those on A (p<0.03 for both). No increase in hip fractures was seen for A vs T (11 vs 13, respectively). To conclude, A showed superior efficacy to T for DFS, TTR and CL BC. These early findings show A as an effective and well-tolerated endocrine option for the treatment of PM pts with EBC. For the first time a choice now exists for AET for PM women with hormone responsive tumours. Longer follow-up will enable a more definitive benefit/risk assessment to be made.