Abstract OT2-6-10: DETECT IV – A multicenter, single arm, phase II study evaluating the efficacy of everolimus in combination with endocrine therapy in patients with HER2-negative, hormone-receptor positive metastatic breast cancer and HER2-negative circulating tumor cells (CTCs)

Abstract

Abstract BACKGROUND: The monitoring of therapy efficacy in metastatic breast cancer (MBC) is a very important component of treatment. Several studies have indicated that the determination of prevalence and number of circulating tumor cells (CTCs) at various times during treatment may be an effective tool for assessing treatment efficacy. Even if the prognostic value of CTCs in MBC is well understood, the role of CTC prevalence and - in particular - CTC phenotype in predicting treatment response requires further investigation. While the recently started DETECT III-trial is designed to evaluate the effect of HER2-targeted therapy in patients with HER2-negative MBC and HER2-postive CTCs, DETECT IV aims to assess the effect of an endocrine treatment in combination with the mTOR-inhibitor everolimus for patients with HER2-negative CTCs. SPECIFIC AIMS/TRIAL DESIGN: DETECT IV is a prospective, multicenter, open-label, single arm phase II study aimed at postmenopausal patients with hormone-receptor positive, HER2-negative metastatic breast cancer. Patients with HER2-negative CTCs will be treated with Everolimus in combination with an endocrine therapy according to the physician's choice (letrozole, anastrozole, exemestan or tamoxifen). The primary objective of the trial is to estimate the clinical efficacy of everolimus in combination with endocrine therapy as assessed by progression-free survival (PFS) in the targeted patient population. Additional research will be done on CTC dynamics and characteristics (e.g. PI3K-mutation-analysis). This will provide a better understanding of prognostic and predictive value of the CTCs. This clinical trial is one more step into a more personalized therapy for metastatic breast cancer and will provide further information on CTCs and their informative value during the therapy. ELIGIBILITY CRITERIA: In this trial postmenopausal female patients suffering from hormone-receptor positive, HER2-negative metastasizing breast cancer with HER2-negative circulating tumor cells (CTC) and indication for standard anticancer therapy will be included. STATISTICAL METHODS/TARGET ACCRUAL: DETECT IV will start in September 2013. The estimated number of patients is 400. Therefore, 2000 patients need to be screened for HER2-negative CTCs. This screening is combined with the DETECT III - trail, which started February 2012. The primary endpoint progression-free survival will be estimated using the Kaplan-Meier method. Prevalence and number of CTCs at various time points will be determined using the FDA-approved CellSearch System (Veridex, USA). In addition, different measures of CTC dynamics and their value for evaluating therapy efficacy or as a prognostic tool will be examined in detail by explorative data analyses. Contact information: fabienne.schochter@uniklinik-ulm.de. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-6-10.