Cardiotoxicity of HER2-targeted therapies

Abstract

Purpose of review-Cardiotoxicity is a well recognized adverse effect of human epidermal growth factor receptor 2 (HER2)-targeted therapies. The goal of this review is to highlight recent studies that have advanced our knowledge of the diagnosis, prevention, and management of cardiotoxicity associated with HER2-targeted agents. Recent findings-Several clinical risk factors for cardiotoxicity associated with HER2-targeted therapies have been identified including age, low-baseline left ventricular ejection fraction, and treatment with anthracyclines; however, these remain insufficient to identify all patients at risk for cardiotoxicity. Routine cardiac monitoring remains the standard for cardiotoxicity surveillance, although the optimal frequency and modality of monitoring remains uncertain. Global longitudinal strain, T1/T2 weighted CMR imaging protocols, and circulating biomarkers can detect early signs of cardiotoxicity, but studies are needed to investigate whether use of these markers in clinical practice improves patient outcomes. Cardioprotective medications (e.g. beta-blockers or ACEinhibitors) may be of benefit to patients at increased risk for cardiotoxicity from HER2-taregeted therapies, particularly those who are treated with an anthracycline-containing regimen. Summary-Improved risk stratification of patients during HER2-targeted therapy and effective prevention and management strategies for cardiotoxicity are needed to enhance the value of longitudinal cardiac monitoring and increase cardiac safety so that optimal breast cancer treatment can be delivered.

Protective Role of Enalapril in Anthracycline-Induced Cardiotoxicity: A Systematic Review

“…A number of studies have shown that global longitudinal strain (GLS) can be used as a predictor of cardiotoxicity and can detect early declines in ventricular mechanics prior to an overt reduction in LVEF (El-Sherbeny et al, 2019;Arciniegas Calle et al, 2018;Potter and Marwick, 2018). In clinical practice, GLS can also help reconcile the significance of asymptomatic fluctuations in LVEF, which occur during serial imaging (Robert et al, 2019). However, it is regrettable that there is still a lack of studies that have evaluated the effect of enalapril on GLS.…”

A First-in-human Phase I Study of TAS0728, an Oral Covalent Binding Inhibitor of HER2, in Patients With Advanced Solid Tumors With HER2 or HER3 Aberrations.

“…Moreover, a fatal instance of cardiac arrest occurred in a patient with no prior history of heart disease and in whom other reasons related to cardiac arrest were not identi ed. Cardiac arrest as a secondary event is not typical of the recognized cardiotoxicity observed during treatment with HER2-targeted therapies, which manifests as decreased left ventricular ejection fraction and/or symptomatic heart failure dysfunction [10]. The etiology of the cardiac arrest event within the current study was unclear, however causal relationship to TAS0728 could not be excluded due to the temporal association observed.…”

Quality of Life and Symptom Management in Advanced Biliary Tract Cancers

“…Overall the reported toxicity profile lapatinib was similar to that of pertuzumab plus trastuzumab [73]. Interestingly, while cardio-toxicity is a well recognized adverse effect of HER2-targeted therapies, adverse cardiac events were not reported in patients with BTC treated with pertuzumab plus trastuzumab or lapatinib in clinical trial [72,73,89].…”