Abstract OT1-1-12: SAFE-HEaRt: A pilot study assessing the cardiac SAFEty of HER2 targeted therapy in patients with HER2 positive breast cancer and reduced left ventricular function
Authors: Lynce F , Barac A , Tan MT , Nunes R , Herbolsheimer P , Isaacs C , Swain SM 
Published: August 2014

Abstract
Background: Substantial benefit of trastuzumab is associated with cardiac side effects, mostly asymptomatic. According to current FDA approved package insert, patients should not receive trastuzumab or newer HER2 targeted therapies if there is evidence of cardiomyopathy.
Trial design: SAFE-HEaRt is a pilot study evaluating the cardiac safety of trastuzumab, pertuzumab and ado-trastuzumab emtansine in 30 patients with HER2 positive breast cancer (BC) and mild LV dysfunction (LVEF≥40% and &lt;50%) while on optimized cardiac therapy with B-Blockers and ACE inhibitors. Left ventricular ejection fraction (LVEF) and myocardial strain will be assessed at baseline, week 6,12,18 and then every 12 weeks. Troponin I (cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) will be collected at the same time points.
Main Eligibility criteria: Patients diagnosed with stage I-IV HER2 positive BC; LVEF≥40% and &lt;50% prior to or while receiving non-lapatinib HER2 targeted therapy.
Specific aims: The primary endpoint is the proportion of patients who complete planned oncologic therapy without the development of a cardiac event (presence of symptoms attributable to heart failure (HF) confirmed by a cardiologist, cardiac arrhythmia requiring pharmacological or electrical treatment, myocardial infarction, sudden cardiac death or death due to myocardial infarct, arrhythmia or HF) or asymptomatic worsening of cardiac function (i.e. asymptomatic decline in LVEF &gt;10% points from baseline and/or LVEF&lt;35% corroborated by a confirmatory echocardiogram in 2-4 weeks).
Additional endpoints include: Median time to development of an event; absolute changes in LVEF during HER2 targeted therapy; HER2 therapy holds attributed to cardiotoxicity; correlation of myocardial strain and serum biomarkers with cardiac events and asymptomatic worsening of cardiac function.
Statistical methods: A two-stage design is used to test if the completion rate of planned oncologic therapy will be at least 30% versus less than 10% with 80% power at a significance level of 5%. At the first stage, 15 patients will be entered. If one or more patients complete therapy in the absence of a cardiac event, then additional 15 patients will be enrolled in the second stage. Early stopping rules are incorporated for safety based on cardiac death and symptomatic HF. Safety monitoring plan consists of an internal cardiac review panel and a Data Safety Monitoring Board (DSMB) that includes an external cardiologist expert.
Present accrual and target accrual: The Institutional Review Board has approved the study. Enrollment of the first patient is expected in July 2013 with a total of 30 patients planned to be recruited. The initial recruitment sites are MedStar Washington Hospital Center and MedStar Georgetown University Hospital. This trial is partially supported by Genentech and funded by a Conquer Cancer Foundation of ASCO Young Investigator Award, supported by The Breast Cancer Research Foundation. Any opinions, findings, and conclusions expressed in this material are those of the author(s) and do not necessarily reflect those of the American Society of Clinical Oncology, the Conquer Cancer Foundation, or The Breast Cancer Research Foundation.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-1-12.