Abstract OT1-3-01: Characterization of circulating tumor cells from subjects with metastatic breast cancer using the CTC-endocrine therapy index: The COMETI-P2-2012.0 trial
Authors: Paoletti C 
Published: August 2014

Abstract
Introduction: Approximately 50% of patients with estrogen receptor (ER) positive metastatic breast cancer (MBC) benefit from endocrine therapy (ET). This percentage is even lower after first line ET. Other than absence of ER, there are no validated markers that predict lack of benefit from ET. Prior studies suggest that relative levels of four markers might predict lack of benefit from ET: low ER and BCL2 and high HER2, and Ki67. Elevated circulating tumor cell (CTC) levels are prognostic in patients with MBC. We have recently demonstrated the ability to quantify ER, BCL2, HER2 and Ki67 on CTC using the CellSearch® system, and we have developed an analytically validated CTC-Endocrine Therapy Index (CTC-ETI). We are now conducting a prospective, multi-institutional clinical trial to test whether pretreatment CTC-ETI predicts lack of benefit from ET, and whether serial CTC-ETI measurements can be used to monitor patients with ER positive MBC starting 2nd or later line of ET.
Objectives: To demonstrate that CTC-ETI can be accurately determined in multiple centers across North America and whether high CTC-ETI is associated with rapid progression (within 3 months of starting ET), and finally to refine the current CTC-ETI algorithm.
Secondary objectives: To determine if changes in CTC-ETI during ET are associated with rapid progression, to correlate the status of the biomarkers on baseline CTC with the status of the same biomarkers in primary and/or metastatic tissue collected from the subjects, and to store CTC positive cartridges for future molecular analyses.
Methods: Women with ER positive, HER2 negative, progressive MBC after one or more lines of ET or during or within 12 months of completing adjuvant ET who are initiating a new ET are eligible. Subjects with brain metastases only or those who are progressing on fulvestrant are not eligible. All subjects must provide written informed consent. Patients may be treated with any approved ET for MBC, and may also receive everolimus. Patients may not be on any investigational therapy. Blood draws (approximately 40 ml) are collected at baseline, at 1, 2, and 3 months after starting therapy, and at 12 months or progression. CTC-ETI is performed as previously described.
Statistical Plan: Enrollment of 200 subjects will provide a sufficient number of evaluable subjects and statistical power for evaluation of the primary and secondary objectives. A total of 120 subjects evaluable for clinical validity analyses will be required to obtain the minimum of 51 subjects with rapid progression for evaluation of the clinical validity of the CTC-ETI. Subjects will be considered evaluable for clinical validity if they have successful calculation of a baseline CTC-ETI and progression status within 3 months of starting ET can be ascertained.
Current Status: The first patient was enrolled in May, 2013, and accrual is ongoing.
Sponsored by Veridex, LLC.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-3-01.