maytansine and Ventricular-Dysfunction--Left

HER2-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.. Patients 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%.. Of 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%.. This 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.

Topics: Ado-Trastuzumab Emtansine; Adrenergic beta-Antagonists; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal, Humanized; Breast Neoplasms; Female; Humans; Maytansine; Middle Aged; Molecular Targeted Therapy; Neoplasm Staging; Pilot Projects; Prospective Studies; Receptor, ErbB-2; Trastuzumab; Treatment Outcome; Ventricular Dysfunction, Left

Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. Current U.S. Food and Drug Administration recommendations limit the use of HER2 targeted agents to patients with normal left ventricular (LV) systolic function.. The objective of the SAFE-HEaRt study is to evaluate the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and mildly reduced left ventricular ejection fraction (LVEF) with optimized cardiac therapy. Thirty patients with histologically confirmed HER2 positive breast cancer (stage I-IV) and reduced LVEF (40% to 49%) who plan to receive HER2 targeted therapy for ≥3 months will be enrolled. Prior to initiation on study, optimization of heart function with beta-blockers and angiotensin converting enzyme inhibitors will be initiated. Patients will be followed by serial echocardiograms and cardiac visits during and 6 months after completion of HER2 targeted therapy. Myocardial strain and blood biomarkers, including cardiac troponin I and high-sensitivity cardiac troponin T, will be examined at baseline and during the study.. LV dysfunction in patients with breast cancer poses cardiac and oncological challenges and limits the use of HER2 targeted therapies and its oncological benefits. Strategies to prevent cardiac dysfunction associated with HER2 targeted therapy have been limited to patients with normal LVEF, thus excluding patients who may receive the highest benefit from those strategies. SAFE-HEaRt is the first prospective pilot study of HER2 targeted therapies in patients with reduced LV function while on optimized cardiac treatment that can provide the basis for clinical practice changes.

Topics: Ado-Trastuzumab Emtansine; Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal, Humanized; Breast Neoplasms; Cardiotoxicity; Echocardiography; Female; Heart; Humans; Maytansine; Middle Aged; Molecular Targeted Therapy; Neoplasm Staging; Receptor, ErbB-2; Trastuzumab; Troponin I; Troponin T; Ventricular Dysfunction, Left

Antibodies against human epidermal growth factor receptor 2 (HER2) affect metastatic breast cancer cells and cardiac myocytes. Guidelines recommend evaluation of cardiac ejection fraction (EF) every 3 months despite little supporting evidence for this need. We assessed the impact of EF screening on clinical practice.. We carried out retrospective analysis of patients with HER2-positive metastatic breast cancer receiving HER2-directed therapy to assess the impact of aggressive cardiac screening on management decisions.. Data for 128 patients were analyzed. The median number of EF screenings in the first year of therapy was 3 (range=1-8). A total of 29 patients had an asymptomatic decrease in EF. These patients had more EF screenings, more exposure to anthracyclines or left-sided radiation, were more likely to receive a cardiology consult and have an angiotensin converting enzyme inhibitor added to their therapy. Ninety patients underwent aggressive screening; this was not associated with cessation of HER2 therapy (p=0.92).. Routine EF screening did not have an impact on decisions regarding HER2 therapy in patients with metastatic breast cancer. Given the known benefit of HER2 treatment, reducing the frequency of cardiac screening may be reasonable.

Topics: Ado-Trastuzumab Emtansine; Adult; Aged; Aged, 80 and over; Anthracyclines; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Breast Neoplasms; Clinical Decision-Making; Echocardiography; Female; Humans; Maytansine; Middle Aged; Receptor, ErbB-2; Stroke Volume; Trastuzumab; Ventricular Dysfunction, Left; Ventricular Function, Left