Abstract OT1-3-02: The treat CTC trial – A new approach targeting circulating tumor cells (CTC) in early breast cancer (EBC)

Abstract

Abstract Background: The presence of CTC in metastatic BC is associated with an impaired prognosis. Recent data show a reduced disease-free survival and increased risk of death in the presence of CTC in EBC. Therefore, patients with persisting CTC after (neo)adjuvant chemotherapy might benefit from additional systemic treatment. Recent data have reinforced the hypothesis that trastuzumab can eliminate tumor cells by antibody dependent cell cytotoxicity (ADCC) or other immune mechanisms. Preclinical data have provided evidence that the benefit of trastuzumab may be associated with targeting cancer stem cells in a HER2 independent model (Ithimakin et al Cancer Res 2013). Trastuzumab eliminated CTC, irrespective of the HER2 status of the primary tumor and of CTC and this was associated with reduced relapses(Georgoulias et al Ann Oncol 2012). Trial Design: Treat CTC trial is a multicenter European randomized phase II trial, sponsored by the EORTC and run under the BIG umbrella. It will assess the efficacy of trastuzumab in eliminating persisting CTC after the completion of (neo)adjuvant chemotherapy and surgery in patients with HER-2-negative EBC. Eligible patients will be randomized in a 1:1 ratio to either 6 cycles of trastuzumab or observation. Patients’ peripheral blood will be tested again for CTC after 18 weeks. Main Eligibility criteria: - Adequately excised HER2-negative EBC - Evidence of CTC detection using the CellSearch technology after completion of (neo)adjuvant chemotherapy - Completion of adjuvant chemotherapy for node-positive disease or neoadjuvant chemotherapy with residual invasive disease in breast or lymph nodes (no complete pathological response) - Histological Grade > 1 and primary tumor size > 1 cm Specific aims: The primaryobjective of the trial is to evaluate whether trastuzumab decreases the detection rate of CTC in patients with HER2-negative EBC by comparing the trastuzumab treated arm to the observation arm. Furthermore, clinical outcomes as measured by Recurrence Free Interval (RFI), Invasive Disease Free Survival (IDFS), Disease Free Survival (DFS) and Overall Survival (OS)) between the trastuzumab and observation arms will be compared. Present accrual and target accrual: Treat CTC started patient screening in April 2013 in Belgium. It is estimated that 2175 women will be registered to include 174 patients eligible for randomization. Accrual is expected to be completed in 2 years. Methods: The primary test will be a one-sided test to compare the trastuzumab arm to the observation arm for the CTC detection rate at week 18 (superiority test). The comparison for the primary endpoint will be performed on the intention-to-treat population using a one-sided test with overall a of 0.1. The odds ratio and its confidence interval will be estimated using a logistic regression model. The comparison of RFI, IDFS, DFS and OS will be done using a two-sided test in a proportional hazards model for cause specific hazard, adjusted for the stratification factors. Perspectives: Given the prognostic relevance of CTC in BC, the Treat CTC trial will be the first multicenter, randomized trial in which CTC are used to guide treatment decisions in EBC. The results of this trial will help to clarify the clinical utility of CTCs in early disease. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-3-02.