Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 525
© 2005 American Society of Clinical Oncology

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rugo, H. S. Articles by Park, J. W. Search for Related Content PubMed Articles by Rugo, H. S. Articles by Park, J. W.

Abstract

Change in circulating endothelial cells (CEC) and tumor cells (CTC) in patients (pts) receiving bevacizumab and erlotinib for metastatic breast cancer (MBC) predicts stable disease at first evaluation

Univ of CA San Francisco, San Francisco, CA; Memorial Sloan-Kettering Cancer Ctr, New York, NY

525

Background: The antivascular effects of antiangiogenic therapy for cancer are not well understood. Identifying clinically relevant intermediate markers for angiogenesis that might predict response has been difficult; CECs have been proposed as a marker of tumor progression and/or response to antiangiogenic therapy with bevacizumab. We performed a phase II study of erlotinib and bevacizumab in pts with MBC based on preclinical data suggesting that EGFR blockade may inhibit angiogenesis, and that combined blockade may increase anti-tumor activity. To explore markers of activity and response, we assayed CECs and CTCs at weeks 0 (baseline), 3, 9, and then Q 9 weeks. 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: 35 of 37 pts have been enrolled. Prelim response data has been reported (Dickler, ASCO 2004). One pt has an ongoing PR at > 72 wks, 4 pts have SD (290, 254, 196, 193d). 27 pts have at least baseline and wk 3 CEC and CTC along with clinical response data. Median CEC level at baseline was 16 CEC/ul (range, 3.7–48.2); CTC levels were 3x less frequent with a median of 0.80 CTC/ml (range, 0–89.2). The magnitude of change in CECs from wk 0 to wk 3 predicted response at first assessment (9 wks) (p = 0.018), as did the magnitude of change in CTCs between the same time points (p=0.01). An increase in CECs over the last two measurements of treatment was associated with PFS (p=0.06). Conclusions: CECs and CTCs may serve as surrogate markers of response and progression, and changes in CEC levels may reflect angiogenic activity. Updated data on the complete study population, as well as serum and tissue markers of angiogenesis will be presented. Supported in part by CTEP and Genentech.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Biooncology

Abstract presentation from the 2005 ASCO Annual Meeting