Abstract S3-3: The UK TACT2 Trial: comparison of standard vs accelerated epirubicin in patients requiring chemotherapy for early breast cancer (EBC) (CRUK/05/019)
Authors: D Cameron, P Barrett-Lee, P Canney, J Banerji, J Bartlett, D Bloomfield, S Bowden, M Brunt, H Earl, P Ellis, M Fletcher, JP Morden, A Robinson, N Sergenson, R Stein, G Velikova, M Verrill, A Wardley, R Coleman, JM Bliss
Journal: Cancer Research (2012)

Abstract Introduction: TACT2, a multicentre randomized phase III trial in patients with node +ve or high risk node -ve invasive EBC with E-CMF as control (Poole NEJM 2006), tests two hypotheses in a 2×2 factorial design: A) accelerated epirubicin (aE) improves outcomes compared to standard epirubicin (E) (CALGB9741 Citron JCO 2003); and B) capecitabine (X) gives similar efficacy but preferential side-effect profile to CMF. Here we focus on the impact of accelerating epirubicin treatment on patient outcome. Tolerability and toxicity of this regimen have already been presented (Cameron 2010, SABCS); 33/4391 pts did not start chemotherapy. 4261 (97%) completed the initial 4 cycles (E 2143 (96%), aE 2118 (98%)) with RDI &amp;gt;85% for E 2061 (93%) and aE 1985 (91%). Serious CTCAE toxicity was less common with aE compared with E, however patients report poorer global QL, fatigue &amp; role function which does not appear to be explained by impact on daily activities due to individual side-effects. Patients &amp; Methods: Between December 2005 and December 2008, 4391 patients (4371 women, 20 men) were randomized to receive either E (100mg/m2 × 4) q3wk or aE (100mg/m2 × 4 plus pegfilgrastim, 6mg d2) q2wk followed by classical CMF q4wk × 4 or X (2500mg/m2/day × 14) q3wk × 4. Other adjuvant treatment was delivered according to local practice (HER2+ve – sequential trastuzumab for 1 year from June 2006; ER/PgR+ve - endocrine therapy for 5 years). Tumor blocks were collected prospectively to enable central biomarker testing. Median age of patients was 52 years (IQR 46–59). 53% patients had node +ve disease; 59% had tumors &amp;gt;2cm; 57% were grade 3. According to local assessment, of 4366 patients where both ER and HER2 status were known, 60% had ER+ve/HER2-ve tumors, 19% HER2+ve, 21% ER-ve/HER2-ve. Primary endpoint was time to recurrence (TTR), defined as time to loco-regional or distant relapse, or breast cancer-death. Secondary endpoints included disease-free survival (DFS), overall survival (OS), tolerability of regimens and quality of life. TACT2 has over 90% power to detect a clinically meaningful 4% difference in TTR between standard and accelerated epirubicin schedules (from 80% to 84% at 5 years). Survival estimates will be compared using stratified log-rank tests and Cox regression. Results: At 1st June 2012, median follow up was 49 months (interquartile range: 46–60) with 553 TTR events reported. The Independent Data Monitoring Committee consider these data sufficiently mature for presentation of analyses relating to the accelerated epirubicin hypothesis. A further data snapshot, after query resolution, for the main analysis will be taken in Q3 2012. Data to be presented, by treatment group, include TTR, DFS, OS, late toxicity and pre-planned subgroup analyses according to ER, PgR and HER2 status and Ki67 levels. Discussion: TACT2 will provide a definitive analysis to confirm or refute benefits previously reported for accelerating anthracycline chemotherapy in early breast cancer including, via pre-planned subgroup analyses, exploration of the potential benefits in phenotypic subtypes. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S3-3.