Abstract OT2-01-03: DETECT V - Comparison of dual HER2-targeted therapy with trastuzumab and pertuzumab plus CDK4/6 inhibition in combination with either chemo- or endocrine therapy in patients with HER2-positive and hormone-receptor positive metastatic breast cancer
Authors: Friedl Thomas WP , Krause Sabrina , Fehm Tanja , Fasching Peter A , Schneeweiss Andreas , Müller Volkmar , Riethdorf Sabine , Pantel Klaus , Taran Florin-Andrei , Polasik Arkadius , Tzschaschel Marie , de Gregorio Amelie , Meier-Stiegen Franziska , Janni Wolfgang , Huober Jens 
Published: March 2020

Abstract
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. However, adverse events are well-known side effects of any cytostatic treatment and can seriously impact the patients’ QoL. Thus, for patients with HER2-positive and hormone-receptor positive MBC, the synergistic combination of dual HER2-targeted therapy with trastuzumab and pertuzumab plus endocrine therapy might offer a better treatment option. Recent 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/CHEVENDO is a randomized phase III study comparing the safety and efficacy of dual HER2 targeted therapy plus 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 choice. The multicenter DETECT V trial started in 2015 in about 120 sites in Germany, and until June 2019 138 patients with HER2-positive, hormone-receptor positive metastatic breast cancer have been enrolled. A sample size of 270 patients is planned.
Specific aims: The primary objective of this study is to compare safety and tolerability of the study treatments between both arms. More specifically, safety will be assessed by the proportion of patients experiencing any adverse event during the treatment period, as defined by a modified adverse event score developed to reflect the clinical and psychological impact of adverse events on the patients’ quality of life. Secondary endpoints are progression free survival, overall survival, and quality-adjusted survival using the quality-adjusted time without symptoms and toxicity (Q-TWiST) method. A translational program is included comprising the detection and phenotyping of circulating tumor cells (CTC) and the assessment of marker expression on CTCs in order to validate an endocrine responsiveness score.
Citation Format: Thomas WP Friedl, Sabrina Krause, Tanja Fehm, Peter A Fasching, Andreas Schneeweiss, Volkmar Müller, Sabine Riethdorf, Klaus Pantel, Florin-Andrei Taran, Arkadius Polasik, Marie Tzschaschel, Amelie de Gregorio, Franziska Meier-Stiegen, Wolfgang Janni, Jens Huober. DETECT V - Comparison of dual HER2-targeted therapy with trastuzumab and pertuzumab plus CDK4/6 inhibition in combination with either chemo- or endocrine therapy in patients with HER2-positive and hormone-receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-01-03.