Randomized, phase III study of adjuvant doxorubicin plus cyclophosphamide (AC) → docetaxel (T) with or without capecitabine (X) in high-risk early breast cancer: Exploratory Ki-67 analyses.

500 Background: First results of study USON 01062 comparing adjuvant AC→T vs AC→XT in high-risk EBC [O’Shaughnessy, SABCS 2010] showed the primary endpoint, improvement in DFS, was not met (median FU 5 yrs: HR 0.84, 95% CI: 0.67–1.05; p%0.125; 304 events), but a statistically significant improvement in OS was seen with AC→XT (HR 0.68, 95% CI: 0.51–0.92; p%0.011; 183 events). Given the current understanding of a lesser benefit of adjuvant chemotherapy in indolent BC, we performed unplanned exploratory subset analyses of Ki-67 expression, distant DFS and benefit from XT. Methods: Pts aged 18–70 yrs with surgically resectable EBC received 4 x 3-weekly AC (A: 60mg/m2, C: 600mg/m2, d1) → 4 x 3-weekly T (100mg/m2 d1) or XT (X: 825mg/m2 bid, d1–14; T: 75mg/m2 d1). ER+ pts received endocrine therapy, and, after 2005, HER2+ pts were offered 1-yr of trastuzumab. Primary endpoint: DFS; secondary endpoints: OS; safety. Ki-67 staining was done locally. Results: 2,611 pts were randomized: AC→T (n%1304); AC→XT (n%1307)....