Abstract OT1-2-02: Trastuzumab in HER2-negative early breast cancer as adjuvant treatment for circulating tumor cells (CTCs) (Treat CTC)
Authors: Ignatiadis Michail , Messina Carlo , Litiere Saskia , Mavroudis Dimitris , Dittrich Christian , Kong Anthony , Janni Wolfgang , Sotiriou Christos , Piccart Martine , Pierga Jean-Yves , Rack Brigitte 
Published: May 2015

Background:

The presence of Circulating Tumor Cells (CTCs) in metastatic breast cancer (BC) is associated with worse clinical outcome. Recent data showed an association between CTC(s) detection and reduced disease-free and overall survival in early disease. Patients with persisting CTC(s) after (neo)adjuvant chemotherapy might benefit from additional systemic treatment.

Trastuzumab is a part of the standard of care for patients with HER2-positive BC. Recent data have reinforced the hypothesis that the therapeutic effect of trastuzumab depends on immune-related mechanisms. It has been demonstrated that trastuzumab eliminated CTC(s), irrespective of the HER2 status of the primary tumor and of CTC(s) and this was associated with improved relapse-free survival (Bozionellou et al, Clin Cancer Res 2004, Georgoulias et al Ann Oncol 2012).

The Treat CTC trial is designed to explore the effect of trastuzumab in patients with HER2-negative early BC and persisting CTC(s) after (neo)adjuvant chemotherapy and surgery.

Trial Design:

Treat CTC trial is a multicentre (6 countries, 92 centers) 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(s) after the completion of (neo)adjuvant chemotherapy and surgery in patients with HER2-negative early BC. Eligible patients will be randomized in a 1:1 ratio to either 6 cycles of trastuzumab or observation.

Eligibility criteria:

- Adequately excised HER2-negative early BC

- Evidence of CTC(s) 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)

Specific aims:

The primary objective is to evaluate whether trastuzumab decreases the detection rate of CTCs in patients with HER2-negative primary BC 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:

It is estimated that 2175 women will be registered to include 174 patients eligible for randomization in a 1:1 ratio. Accrual is expected to be completed in 2 years. Treat CTC started patient screening in May 2013 in Belgium, in March 2014 in Germany and in June 2014 in France. An update of the proportion of patients screened versus patients randomized will be presented during SABCS.

Methods:

The primary test will be a one-sided test to compare the trastuzumab arm to the observation arm for the CTC(s) 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 α 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.

Citation Format: Michail Ignatiadis, Carlo Messina, Saskia Litiere, Dimitris Mavroudis, Christian Dittrich, Anthony Kong, Wolfgang Janni, Christos Sotiriou, Martine Piccart, Jean-Yves Pierga, Brigitte Rack. Trastuzumab in HER2-negative early breast cancer as adjuvant treatment for circulating tumor cells (CTCs) (Treat CTC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-2-02.