P1-18-01: Z-ACT1: Zometa Combined with Standard Therapy in Patients with Metastatic Breast Cancer Further Decreases the Proportion of Patients with CTC Counts of 5 or above.
Authors: A Brufsky, J Beck, S Dakhil, S Hallmeyer, H Tezcan, D Yardley, D Tran, G Warsi, K Culver
Journal: Cancer Research (2011)

Abstract Introduction: Zoledronic acid (ZOL) has been shown to reduce the risk of recurrence and residual tumor size in the adjuvant/neoadjuvant setting in patients with early/intermediate-stage breast cancer (BC). In addition, ZOL combined with neoadjuvant chemotherapy reduced numbers of disseminated-tumor cells in the bone marrow compared with chemotherapy alone. However, the activity of ZOL on disseminated- or circulating-tumor cells (CTCs) in patients with metastatic breast cancer (MBC) is not well defined. Cristofanilli M, et al (J Clin Oncol. 2005; 23: 1420–30) reported that CTCs in MBC are an independent predictor of overall survival (OS) and progressionfree survival (PFS). Accordingly, this study is evaluating the potential anticancer benefit of adding ZOL to standard therapy in patients with newly diagnosed MBC as assessed by the change in CTC count from baseline to 3–5 weeks. Methods: Eligible patients had HER2−negative MBC, newly diagnosed or at first relapse after adjuvant therapy with or without bone metastases. In this open-label 3-arm study, patients without bone metastases were randomized to standard therapy + ZOL every 3–4 weeks for the first 6 months (Arm A) or standard therapy + ZOL during month 6–12 after standard therapy initiation (Arm B). All patients with bone metastases received ZOL every 3–4 weeks (Arm C). The primary endpoint is PFS. Secondary endpoints include the proportion of patients with CTCs ≥5 or &amp;lt;5 per 7.5 mL of peripheral blood 3–5 weeks after standard therapy initiation. Data were compared with historical controls (patients with MBC receiving first-line standard treatment alone; Cristofanilli M, et al. 2005). CTCs were quantified using CellSearch™. Results: In Z-ACT1, 29 previously untreated MBC patients with bone metastases were enrolled in Arm C, all of whom had ≥1 CTC at study entry (range, 1–117). 53% received hormonal therapy alone, 42% chemotherapy alone, and 5% received various combinations. In patients receiving standard therapy + ZOL, the percentage of patients with CTC ≥5 decreased from 55% to 25% at 3–5 weeks. At baseline, the median uNTX level was 46.5 (n = 10) in patients with &amp;lt; 5 CTCs and 57 in patients with ≥5 CTC (n = 13). At 3–5 weeks, the median decrease from baseline in uNTX was 74% (n = 10) in the &amp;lt; 5 CTC group and 25% (n = 5) in the ≥5 CTC group. At 3–5 weeks, the median uNTX levels in the &amp;lt;5 and ≥5 CTC groups were 12 and 22 nmol bce/mmol, respectively. This study has now been modified to a 2-arm study (standard therapy +/− ZOL) in MBC patients with no bone metastases. CTC, uNTX, and PFS data will be presented from this new head-to-head analysis. Changes in CTCs out to 6 months and correlation with uNTX and PFS in this original bone metastasis cohort will also be presented. Conclusions: This preliminary analysis suggests that the addition of ZOL to standard therapy in women with bone metastases from MBC results in a further decrease in CTC numbers at 3–5 weeks after initiation of therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-18-01.