PURPOSE Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. PATIENTS AND METHODS Eligible patients were those with operable, node-positive—or node negative with tumor 1 cm or greater—TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. RESULTS Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P = .136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P = .0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P = .0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. CONCLUSION This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation.

570 Introduction: Capecitabine (Xeloda [X]) shows synergy with taxanes and adding X to docetaxel (T) extends overall survival (OS), response rate (RR) and progression free-survival (PFS) beyond T alone. Sequential single-agent therapy could confer convenience benefits and may be more appropriate than combination chemotherapy for some pts. Methods: Pts with anthracycline-pretreated MBC received 3-weekly cycles of 1 of the following regimens: X→taxane (X 1250mg/m2 bid d1–14, followed after progression (PD) by T 100mg/m2 or paclitaxel [P] 175mg/m2 day 1; X+P (X 825mg/m2 bid days 1–14 + P 175mg/m2 day 1) or X+T (X 825mg/m2 bid days 1–14 + T 75mg/m2 day 1). Results: Of the 368 pts enrolled, 91 are either still on therapy or not evaluable. The table shows baseline characteristics, efficacy and safety in evaluable pts. Median follow up is 15.5 months. Median doses for X in each arm (1st cycle vs. 8th cycle, mg/m2 bid): 1218 vs. 1054; 948 vs. 900; 846 vs. 751. Median doses for P and T (1st cycle vs. 8th cycle, mg/m2): 173 vs. 169 and 75 vs. 72, respectively. In the X→taxane arm, 58 pts (64%) received sequential taxane; the remainder did not receive a taxane, either because they were still on X, had CR or had rapid PD. Conclusions: RR is higher with XP and XT, but PFS and OS are similar at a median follow-up of 15.5 months. All regimens were well tolerated with minimal grade 4 AEs. Because there is no clear superiority of sequential vs. combined therapy, pt characteristics are likely to be used to decide which regimen is the most appropriate. [Table: see text] [Table: see text]

Background: A large adjuvant trial programme is exploring the role of capecitabine (C) in early breast cancer (EBC). CIBOMA 2004-01/GEICAM 2003-11 is a multicenter, international randomised phase III trial that focuses on adjuvant C maintenance therapy after conventional induction chemotherapy in triple-negative EBC. Here we report interim safety data from the trial. Materials and methods: Patients (pts) with operable, node-positive (or node-negative with tumour diameter ≥1 cm), hormone receptor-negative, HER2-negative EBC (central laboratory confirmation) who have received standard anthracycline-and/or taxane-containing chemotherapy in the (neo)adjuvant setting are eligible. Pts are randomised to receive 8 cycles of C (1000 mg/m2 bid, d1-14 q21d) (Arm A) or observation (Arm B). The primary endpoint is disease-free survival (DFS). Assuming 30% risk reduction in DFS rate at 5 years (from 64.7% to 73.7%, HR of 0.701) with a power of 80% and a two-tailed log-rank test at 0.05, 834 evaluable patients will be needed. With an expected drop-out rate of 5%, 876 pts will be included. We anticipate completing recruitment by the end of 2010. Efficacy analysis will be triggered after 255 events. Results: To date, 724 pts have been recruited; here we report safety data from the first 278 pts (136 in Arm A and 142 in Arm B). Baseline characteristics are well balanced between the treatment arms. Baseline Characteristics In total, 920 cycles of C were administered (median 8.0, range 0-8). All 8 cycles were completed by 74.3% of pts. Median relative dose-intensity of C was 91.1%. The most common grade 3/4 clinical AEs related to C were: hand-foot syndrome (Grade 3 19.1%), diarrhoea (3.0%), vomiting (1.5%), fatigue (1.5%), nail changes (1.5%) and bilirubin elevation (1.5%). Conclusions: The safety profile of adjuvant C as maintenance therapy is consistent with its known toxicity profile. Safety data from the first 400 randomised pts will be reviewed by an Independent Data Monitoring Committee and used to update this analysis at the meeting. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-15.