Abstract OT3-04-02: DETECT III and IV – Individualized CTC-based therapy of metastatic breast cancer

Abstract

Abstract Background: Circulating tumor cells (CTCs) are found in patients with early and metastatic breast cancer (MBC), and both their prognostic and predictive value has been described already. There is growing evidence that CTC phenotype may differ from the primary tumor. However, CTC targeted therapy is not used in clinical routine, and treatment decisions often still are based on the primary tumor's phenotype without considering CTC-characteristics. The aim of the DETECT studies is to investigate and evaluate the role of presence and phenotype of CTC for guiding therapeutic decisions in women with HER2-negative MBC. Trial design and eligibility criteria: In a joint screening for DETECT III and IV, women with HER2-negative MBC are tested for CTCs and their HER2-phenotype. CTC detection is performed by the FDA-approved CellSearch System® (Janssen Diagnostics, Raritan, USA). Patients with HER2-positive CTCs are randomized in the multicenter Phase III study DETECT III to a physician's choice chemo- or endocrine therapy with or without additional HER2-targeted treatment with lapatinib. Women with only HER2-negative CTCs are recruited to the multicenter open-label phase II study DETECT IV. Postmenopausal women with hormone-receptor positive MBC are treated with everolimus and a physician's choice endocrine therapy in DETECT IVa. Patients with hormone-receptor positive MBC and an indication for chemotherapy and patients with triple-negative MBC receive mono-chemotherapy with eribulin in DETECT IVb. Treatment efficacy will be evaluated based on the early available CTC clearance rate (in DETECT III and DETECT IVa) and progression-free survival (in DETECT IVb) respectively, as the primary endpoint; secondary objectives will be to estimate disease control rate, progression-free (DETECT III and IVa) and overall survival, toxicity and tolerability of treatments with lapatinib, everolimus and eribulin, and quality of life. Specific aims: Changes in CTC-dynamics during therapy and their HER2-phenotype may influence following therapy decisions. The DETECT studies evaluate the prognostic and predictive role of CTCs as well as the efficacy of CTC based therapy to enable the establishment of a more personalized therapy for patients with MBC that might lead to prolonged progressive free survival and/or improved quality of life. The accompanying translational research programs investigate various markers for molecular characterization of CTCs and prediction of therapy response. Present accrual and target accrual: More than 1550 patients with HER2-negative MBC have already been screened within the DETECT study program. Thus, it is the worldwide largest study concept with therapy decisions resulting from CTC-testing and CTC-phenotypization. Contact: For further information on the DETECT study program please contact www.detect-studien.de or studienzentrale.ufk@uniklinik-ulm.de. Citation Format: Polasik A, Schramm A, Friedl TWP, Rack B, Trapp E, Fasching PA, Taran F-A, Hartkopf A, Schneeweiss A, Müller V, Aktas B, Pantel K, Meier-Stiegen F, Wimberger P, Janni W, Fehm T. DETECT III and IV – Individualized CTC-based therapy of metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-04-02.