Abstract OT2-07-01: DETECT V/CHEVENDO – Comparison of dual HER2-targeted therapy with trastuzumab plus pertuzumab in combination with chemo- or endocrine therapy in addition with CDK4/6 inhibition in patients with HER2-positive and hormone-receptor positive metastatic breast cancer

Background: Metastatic breast cancer (MBC) is usually an incurable disease and maintenance of quality of life (QoL) is one of the main aims of therapy. In patients with HER2-positive MBC taxane-based chemotherapy in combination with dual HER2 targeted therapy with trastuzumab and pertuzumab,is the standard of care. Adverse events are well-known side effects of any cytostatic treatment and can seriously impact the patients9 QoL. The synergistic combination of dual HER2-targeted therapy with trastuzumab and pertuzumab plus endocrine therapy might offer a better treatment option for these patients. First clinical trials suggest an additional benefit when a CDK4/6 inhibitor is added to the combination of endocrine therapy and anti HER2 treatment. DETECT V is a randomized phase III study comparing the safety and efficacy of trastuzumab plus pertuzumab and the CDK 4/6 inhibitor ribociclib in combination with either endocrine therapy or chemotherapy. Trial design: Patients with HER2 positive and hormone-receptor positive MBC are 1:1 randomized to receive trastuzumab and pertuzumab combined with endocrine therapy and ribociclib or to chemotherapy with trastuzumab and pertuzumab followed by maintenance therapy with trastuzumab, pertuzumab, endocrine therapy and ribociclib. Chemotherapy and the endocrine agents can be chosen from a variety of available regimens according to the physicians discretion. Specific aims: The primary objective of this study is to compare safety and tolerability in both arms, as assessed by the occurrence of AEs during the treatment period. Secondary endpoints are progression free survival, overall survival, quality-adjusted survival using the quality-adjusted time without symptoms and toxicity (Q-TWiST) method. A translational program is included investigating detection and phenotyping of circulating tumor cells (CTC)-and the assessment of marker expression on CTCs in order to validate an endocrine responsiveness score. Present accrual and target accrual: The DETECT V trial started 2015 in the Dept. of Gynecology, University of Ulm and at the up to 120 sites in Germany. Until June 2018 97 patients with HER2-positive, hormone-receptor positive metastatic breast cancer have been enrolled. A sample size of 270 patients is planned. Contact information: Jens Huober, University of Ulm, Dept of Gynecology, Breast Center, jens.huober@uniklinik-ulm.de Sabrina Krause, University of Ulm, Dept of Gynecology, sabrina.krause@uniklinik-ulm.de Citation Format: Krause S, Friedl T, Fehm T, Romashova T, Fasching PA, Schneeweiss A, Muller V, Taran F-A, Polasik A, Tzschaschel M, De Gregorio A, Meier-Stiegen F, Janni W, Huober J. DETECT V/CHEVENDO – Comparison of dual HER2-targeted therapy with trastuzumab plus pertuzumab in combination with chemo- or endocrine therapy in addition with CDK4/6 inhibition in patients with HER2-positive and hormone-receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-07-01.