Abstract P5-10-07: TACT2 Randomised Adjuvant Trial in Early Breast Cancer (EBC): Tolerability and Toxicity of Standard 3 Weekly Epirubicin (E) Versus Accelerated Epirubicin (aE) Followed by Capecitabine (X) or CMF in 129 UK Hospitals (CRUK/05/019)

Introduction: TACT2, a multicentre phase III trial with E-CMF as control (NEAT Poole NEJM 2006), tests 2 hypotheses in a 2x2 factorial design: A) accelerating chemotherapy (CT) offers superior benefits (CALGB9741 Citron JCO 2003); B) the oral 5FU prodrug X gives similar efficacy but preferential side-effect profile to CMF. Here, focus is on hypothesis B with results for compliance, QL & acute toxicities (physician & patient (pt) reported) during CMF vs. X Materials & Methods: 4391 pts (4371 women, 20 men) with node+ve/high risk node-ve invasive EBC were recruited between Dec 2005-08. Treatment was E(100mg/m 2 x 4) q3wk vs q2wk aE(100mg/m2 x 4 + pegfilgrastim 6mg d2) followed by classical CMF q4wk x 4 vs X(2500mg/m 2 /day x 14) q3wk x 4. Detailed CTCAE toxicity was assessed in a subset (38 centres, 2086 pts receiving ≥1 cycle CMF or X). 1279/2086 also participated in substudy of pt-reported outcomes (EORTC QLQ-C30 and TACT2-specific toxicities). 826 had complete dataset (baseline, cycles 4&8). P-values are trend tests across all grades & %grade 3+ are reported. QL assessed via linear regression models adjusted for baseline, end cycle 4 score, & aE vs E. P QL in cycles 5-8 was better with X than CMF for global QL& fatigue (P 10 points): global QL CMF 106/398 (27%), X 79/428 (18%); fatigue CMF 164/398 (41%), X 122/428 (29%)). Conclusion: TACT2, the largest adjuvant EBC trial with X, confirms that X has preferential side-effect profile and global QL compared to CMF, with no evidence that prior aE compromised treatment delivery. Dose delivery data are consistent with advanced disease observations that for some pts, 2000mg/m 2 /day may be correct dose. Results: 4264 (97%) pts continued on CT beyond cycle 4. 3726 completed all 8 cycles (E-CMF 951 (85%), aE-CMF 938 (86%), E-X 932 (84%), aE-X 905 (83%). For cycles 5-8, %RDI > 85% was 69% after E and 68% after aE. Cycles delivered on time CMF 59%, X 63%; cycles without dose reduction CMF 75%, X 62%. 15 deaths in total within 30 days of CT: 9 on CMF, 6 on X. Worst grade toxicities which differed between CMF & X during cycles 5-8: Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-07.