Abstract OT1-03-05: The DETECT V-Study – 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
Authors: Romashova T , Polasik A , Friedl TWP , Rack B , Tzschaschel M , Fasching PA , Taran F-A , Hartkopf A , Schneeweiss A , Mueller V , Bahriye A , Pantel K , Meier-Stiegen F , Wimberger P , Janni W , Fehm T , Huober J 
Published: February 2018

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, has shown significantly increased progression free survival and overall survival. Adverse events are well-known side effects of any cytostatic treatment and can seriously impact the patients' 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. Preclinical data and first clinical trial results 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 in combination with either endocrine therapy or chemotherapy. In both treatment arms the CDK4/6 inhibitor ribociclib will be added.
Trial design and eligibility criteria: Patients are 1:1 randomized to receive dual HER2-targeted therapy with 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 when chemotherapy has stopped.
The sample size calculations are based on the assumption that the probability of having an adverse event as defined by the modified adverse event score for patients with HER2 positive metastatic breast cancer in the chemotherapy arm is 86.3%. Based on this assumption, a minimum of 121 patients per treatment arm is required to detect a 25% decreased risk of having an adverse event as defined by the modified adverse event score (i.e. a relative risk ratio of 0.75) for patients treated with dual HER2-targeted plus endocrine therapy and ribociclib as compared to patients treated with dual HER2-targeted plus chemotherapy with the combination of endocrine therapy and ribociclib as maintenance treatment (90% power, two-sided test, α = 0.05).
Specific aims: The primary objective of this study is to assess the tolerability of both treatment strategies, as assessed by the occurrence of AEs during the treatment period. Modified adverse event score was developed in order to better reflect the clinical, physiological and psychological impact of AEs on patients' QoL. Key secondary endpoint, besides the efficacy endpoints progression free survival (PFS) and overall survival, is to compare quality-adjusted survival (QAS), as measured using the quality-adjusted time without symptoms and toxicity (Q-TWiST) method, between both treatment arms.
The DETECT V trial comes along with a comprehensive translational program focusing on detection and phenotyping of circulating tumor cell (CTC)-and the assessment of marker expression on CTCs in order to calculate an endocrine responsiveness score.
Citation Format: Romashova T, Polasik A, Friedl TWP, Rack B, Tzschaschel M, Fasching PA, Taran F-A, Hartkopf A, Schneeweiss A, Mueller V, Bahriye A, Pantel K, Meier-Stiegen F, Wimberger P, Janni W, Fehm T, Huober J. The DETECT V-Study – 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 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-03-05.