The National Epirubicin Adjuvant Trial (NEAT) and Scottish Cancer Trials Breast Group (SCTBG) br9601 randomized phase III adjuvant early breast cancer trials: The updated definitive joint analysis

534 Background: NEAT and the SCTBG BR9601 trial address the role of Epirubicin (E) as an adjunct to CMF in adjuvant chemotherapy for women with early breast cancer (EBC). Methods: NEAT compared E (100mg/m2 x4cycles) followed by classical (c)CMF (x4cycles) with cCMF (x6cycles); BR9601 compared E (100mg/m2 × 4cycles) followed by iv dose modified CMF q3w (750:50:600 ×4cycles) with iv CMF (x8cycles). Eligibility was completely excised EBC, requiring adjuvant chemotherapy, and start of treatment <10 wks from surgery. Primary outcome measures were relapse-free-survival (RFS) and overall survival (OS). A joint efficacy analysis of NEAT (n=2,021) and BR9601 (n=370) triggered by planned 5-year median follow-up (FU) and estimated 800 RFS events and 600 deaths has 85% power to detect 5% two-sided differences. Results: In 2,391 eligible patients, characteristics were balanced across treatments: 72% node +ve; 59% <50 years old; 47% pre-menopausal; 58% tumours grade 3; 55% >2cms; 32% ER-ve, 50% ER+ve (18% NA). At a median FU of 6.2 yrs, 710 relapses or deaths without relapse and 570 deaths are observed. Despite lower than anticipated event rates in the control arm, these updated results confirm a highly significant benefit in favour of ECMF for both RFS (HR 0.75 (95%CI 0.64–0.87) p=0.0002) and OS (HR 0.74 (0.62–0.87) p=0.0004), independent of trial and prognostic factors. In 1458 NEAT patients (in whom data are available), 68% were to receive tamoxifen; chemotherapy scheduling data is available for 843, of whom 46% were declared concurrent and 54% sequential. In a non-pre-planned retrospective analysis, sequential tamoxifen shows a trend for advantage on RFS (HR 0.78 (0.59–1.02) p=0.06). We have amenorrhoea data on 598 NEAT and BR9601 pre-menopausal women, of whom 72% became amenorrhoeic by the end of chemotherapy. In this instance, developing amenorrhoea showed no advantage for RFS (HR 0.90 (0.65–1.24) or OS (HR 0.99 (0.68–1.44)). Conclusions: This updated definitive analysis adds to the Overview in respect of an anthracycline advantage and confirms ECMF as an established and effective standard adjuvant therapy for EBC. [Table: see text]