In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 18_suppl ( 2006-06-20), p. 3039-3039
Abstract:
3039 Background: Antiangiogenic therapy has demonstrated efficacy in the treatment (tx) of metastatic breast cancer. Mechanism-based biomarkers of antiangiogenic therapy, if clinically validated, offer the potential to optimize this novel therapy. CECs have been proposed as a marker of tumor progression and/or response to antiangiogenic therapy with B. We performed a feasibility study testing B combined with L for the tx of hormone receptor-positive MBC. To explore markers of activity and response, we assayed CECs and circulating tumor cells (CTCs) at weeks (wks) 0 (baseline), 3, 12, and then Q 12 wks. Methods: CECs were defined as CD34/31+, CD45-. Progenitor (CD133+) (CECp) and activation markers (CD106+) were also measured. For CECs, 50 ul of blood was stained with the indicated MAbs; after RBC lysis, flow cytometry (FC) was performed for total CEC and CECp. For CTCs, 20 ml of blood was subjected to immunomagnetic capture using anti-EpCAM ferrofluid, followed by FC for EpCAM, CD45, and nucleic acid content. The log rank test was used to test for significant differences related to response. Results: 32 of 42 pts have been enrolled. As separately reported, prior non-steroidal AI (NSAI) use without progression is permitted; median (med) time on L before start of B was 6 mo (1–52). 28 pts have at least baseline and week 3 CEC and CTC along with clinical response data. Med CEC level at baseline was 10.4 CEC/ul (4–38); the peak value at any time point was 107. CTC levels were much less frequent with a med of 0.3 CTC/ml (0–95, and highest value 1153). An increase in CECs at wk 3 compared to wk 0 predicted worse PFS (p = 0.015). CTCs were ≤ 0.1 at study start in 40% of pts and ≥ 1.0 in only 17%, likely due to length of prior L; change in values at wk 3 did not correlate with PFS in this pretreated group. Conclusions: Consistent with our previous results in a separate trial of B containing treatment in MBC, changes in CEC levels appear to be a biomarker of response/progression on antiangiogenic therapy. CTCs did not reflect response or progression in this population of patients, likely due to lengthy prior exposure to letrozole. Supported in part by Genentech and Novartis. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2006.24.18_suppl.3039
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2006
detail.hit.zdb_id:
2005181-5
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