Abstract
PurposeHER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction.MethodsPatients with stage I–IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40–49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%.ResultsOf 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%.ConclusionThis study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.
Highlights
The initial trials of trastuzumab for metastatic breast cancer revealed increased risk of cardiac toxicity with rates of left ventricular ejection fraction (LVEF) decline ranging from 3 to 27% [1]
Subsequent trials leading to the approval of human epidermal growth factor receptor 2 (HER2)-targeted therapies have employed stringent cardiovascular eligibility criteria, cardiac monitoring schema, and early stopping rules largely based on LV function assessed by LVEF [2,3,4,5,6,7,8]
The SAFE-HEaRt trial is the first prospective study to demonstrate safety of HER2-targeted therapies in patients with reduced cardiac function defined as LVEF between 40 and 49% with concomitant treatment with carvedilol and reninangiotensin inhibitors
Summary
The initial trials of trastuzumab for metastatic breast cancer revealed increased risk of cardiac toxicity with rates of left ventricular ejection fraction (LVEF) decline ranging from 3 to 27% [1]. In the adjuvant trastuzumab clinical trials, up to 18% of patients had asymptomatic declines in LVEF and in one study 19% discontinued trastuzumab, the observed rates of clinical heart failure (HF) were low. The SAFE-HEaRt study (ClinicalTrials.gov, Identifier: NCT01904903) is the first prospective study to test the hypothesis that trastuzumab, pertuzumab and T-DM1 can safely be used in patients with compromised LV systolic function, along with cardiac monitoring and treatment with cardioprotective agents [19]. This group of patients at present have limited oncologic treatment options, and are at risk for adverse cancer outcomes
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