Abstract P1-13-03: Mature analysis of UK Taxotere as Adjuvant Chemotherapy (TACT) trial (CRUK 01/001); effects of treatment and characterisation of patterns of breast cancer relapse.

Abstract

Abstract Introduction: TACT, an investigator-led study in 4162 women with node positive (N+ve) or high risk node negative (N-ve) early breast cancer (EBC), is the largest taxane trial unconfounded by treatment (trt) duration. At principal analysis, with 5 years follow-up (fup), no evidence of improved disease-free survival (DFS) was observed by switching to 4 cycles of docetaxel (D) after 4 cycles of FEC (Ellis, Lancet 2009). Results were provocative in suggesting differential effects according to ER & HER2 status. Longer fup provides opportunity to detect emergence of late trt effects overall & within phenotypic subgroups & explore patterns of recurrence, by tumor characteristics. Patients & methods: TACT recruited women with histologically confirmed completely resected invasive EBC from 104 centers (UK (103), Belgium (1)) between 02/2001 & 07/2003. Centers chose FEC (600/60/600 mg/m2 q3wk × 8) or E-CMF (E 100mg/m2 q3wk × 4 → CMF 100mg/m2 PO d1-14 or 600mg/m2 IV d1&8/40/600 mg/m2 q4wk × 4) as their control, reflecting standard UK practice. Patients (pts) were randomized to FEC-D (FEC q3wk × 4 → D 100 mg/m2 q3wk × 4) or control. 2523 pts were from FEC centers (FEC = 1265: FEC-D = 1258) & 1639 from E-CMF centers (E-CMF = 824; FEC-D = 815). Endocrine therapy was given for 5 years. Few pts received HER2 directed therapy; 589 pts had unknown HER2 status. Median fup is now 97.5 months; this analysis updates DFS & overall survival in the ITT population. It also explores patterns of relapse by phenotypic & clinical characteristics. Analyses of trt effect are stratified by ER status due to issues of non-proportionality of hazard associated with length of fup. Results: DFS events have been reported for 1329 pts (FEC-D=640, Control=689) giving an unadjusted hazard ratio (HR) & 95%CI (stratified by control regimen & ER status) of 0.93 (0.83, 1.03) overall; p = 0.16 in favor of FEC-D & for ER+ve/HER2-ve of 0.99 (0.84, 1.17), for ER+ve/HER2+ve) 0.97 (0.73, 1.30), for ER-ve/HER2+ve 0.74 (0.53, 1.03), & ER-ve/HER2-ve 0.93 (0.73, 1.17). 1017 patients have died (FEC-D=500, Control=517); unadjusted HR=0.98 (95%CI: 0.86, 1.10); p = 0.69 with intercurrent deaths (prior to distant relapse) reported for 80 pts (FEC-D=40, Control=40). Annual event rates show different pattern of disease relapse by phenotypic subgroup Graphical representation will further explore these patterns & associated sites of relapse. Discussion: With a median fup of >8 years no clear benefit has emerged for D over standard anthracyclines within the TACT pt group. Differential effects associated with different patterns of relapse remain of interest. TACT precedes use of antiHER2 therapy which is known to have impacted on early relapse risk in HER2+ve pts. The high relapse risk observed for pts with ER-ve/HER2-ve disease remains a current clinical challenge. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-03.