CHICAGO—Exploratory Ki-67 analyses suggest the benefit of capecitabine use against more highly proliferative tumors, which reflects the importance of patient selection in adjuvant trials, investigators reported at the American Society of Clinical Oncology’s 2011 Annual Meeting.

John E. Pippen, MD, FACP, of Baylor Sammons Cancer Center, Texas Oncology US Oncology, Dallas, and colleagues established the primary endpoint of improvement in disease-free survival (DFS), which was not met (HR 0.84; P=0.125), and secondary endpoints of overall survival (OS) and safety in this randomized, multicenter, Phase 3 trial. Ki-67 staining was done locally.

Patients aged 18–70 years with surgically resectable early breast cancer received 4 x 3-weekly adjuvant doxorubicin 60mg/m2 + cyclophosphamide 600mg/m2 (AC) (Day 1) followed by either 4 x 3-weekly doxetaxel (T) 100mg/m2 (Day 1) or capecitabine 825mg/m2 twice daily (Days 1–14) + docetaxel 75mg/m2 (XT) (Day 1). Estrogen receptor (ER+) patients received endocrine therapy; after ASCO 2005, HER2+ patients were offered 1 year of trastuzumab. Of the 2,611 patients enrolled in the trial, 1,304 were randomized to receive AC followed by T and 1,307 received AC followed by XT. Treatment arms were balanced.

Exploratory distant DFS analysis favored the XT group (HR 0.84 [95% CI, 0.67–1.05]). Analyses by Ki-67 expression showed a treatment effect with XT vs. T in patients with Ki-67 ≥10% (HR for DFS=0.70 [0.50–0.98]; OS: 0.52 [0.33–0.82]). Very few events (DFS/OS) were seen in patients with Ki-67 <10%, with no difference in DFS with XT vs. T. In patients with ER+/HER2- tumors and Ki-67 ≥10%, a trend towards DFS (HR=0.66 [0.38–1.13]) and OS (0.30 [0.11–0.81]) benefit with XT was also seen.