Abstract OT1-2-03: The DETECT-study concept: Treatment based on the phenotype of circulating tumor cells in HER2-negative metastatic breast cancer
Authors: Jaeger Bernadette AS , Albrecht Susanne , Schochter Fabienne , Melcher Carola A , Hagenbeck Carsten , Friedl Thomas WP , Rack Brigitte , Müller Volkmar , Fasching Peter A , Janni Wolfgang , Fehm Tanja 
Published: May 2015

Abstract
Background: The prognostic impact of circulating tumor cells (CTC) in metastatic breast cancer (MBC) is well demonstrated. The role of CTCs in predicting specific treatment response and the importance of CTC phenotypes for therapeutic decisions will be investigated within the DETECT-study concept.
Trial Design and eligibility criteria: The DETECT studies are prospective, multicenter, open-label clinical trials designed for patients with HER2-negative MBC and evidence of CTCs in the peripheral blood. DETECT III is a two-arm study for patients with HER2-positve CTCs, randomized to physician’s choice therapy (chemotherapy or endocrine treatment) with or without additional HER2-targeted treatment with lapatinib. DETECT IV combines tow single-arm studies aimed at patients with HER2-negative CTCs. Postmenopausal patients with hormone-receptor-positive MBC will be treated with the mTOR-inhibitor everolimus in combination with an endocrine therapy of physician’s choice (everolimus cohort), whereas patients with triple-negative or hormone-receptor-positive MBC and indication to chemotherapy will receive eribulin (eribulin cohort).
Specific aims: The primary objective of the trials is to estimate the clinical efficacy of treatments, assessed by the CTC clearance rate for DETECT III and by progression-free survival (PFS) for DETECT IV.
Methods: Prevalence of CTCs at various time points as well as the HER2 status of CTCs are assessed using the FDA-approved CellSearch System (Veridex, USA). After immunomagnetic enrichment with an anti-EpCam-antibody, cells were labelled with anti-CK8/18/19 and anti-CD45 antibodies to distinguish epithelial cells from leucocytes. A fluorescein conjugate antibody with anti-CK-Fluorescein Isothiocyanate (FITC) was used for HER2 phenotyping. The cut-off for CTC-positivity was 1 CTC and for HER2 1 CTC with strong HER2-staining (+++). Survival endpoints will be estimated using the Kaplan-Meier method.
Present and target accrual: Overall, about 2000 patients with HER2-negative MBC will have to be screened for CTCs to be able to recruit 228 patients with HER2-positive CTCs for DETECT III (which started in February 2012), 400 patients with HER2-negative CTCs for DETECT IV- everolimus cohort (which started in December 2013) and 120 patients for DETECT IV- eribulin cohort (which will start in the second half of 2014). 907 patients have been recruited for CTC screening until June 2014.
Perspectives: One screening for CTCs offers different treatment options for patients with HER2-negative MBC and evidence of CTCs within the DETECT-study concept. DETEC III is the first study to investigate a personalized targeted treatment based on the phenotype of CTCs. The addition of a HER2-targeted therapy in case of HER2-positive CTCs is innovative and in case of success will lead to new treatment strategies in MBC. DETECT IV complements DETECT III with regard to additional therapy indications.
Citation Format: Bernadette AS Jaeger, Susanne Albrecht, Fabienne Schochter, Carola A Melcher, Carsten Hagenbeck, Thomas WP Friedl, Brigitte Rack, Volkmar Müller, Peter A Fasching, Wolfgang Janni, Tanja Fehm. The DETECT-study concept: Treatment based on the phenotype of circulating tumor cells in HER2-negative metastatic breast cancer [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 OT1-2-03.