Should a cardioechoscopy (echocardiogram) be performed before initiating treatment with Enhertu (trastuzumab deruxtecan)?

From the Guidelines

Yes, a cardioechoscopy (echocardiogram) should be performed before initiating treatment with Enhertu (trastuzumab deruxtecan). This baseline cardiac assessment is crucial because Enhertu carries a risk of cardiotoxicity, including left ventricular dysfunction and heart failure, as noted in the management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations 1. The recommended approach is to obtain a baseline echocardiogram to assess left ventricular ejection fraction (LVEF) prior to starting treatment, with periodic monitoring during therapy.

Key Considerations

• Patients should have an LVEF within normal range (typically ≥50%) before beginning Enhertu.
• The cardiotoxicity risk stems from the HER2-targeted component of the medication, as HER2 receptors are present in cardiac tissue and their inhibition can affect cardiac function.
• This risk is particularly important in patients with pre-existing cardiac conditions or those who have received prior cardiotoxic therapies such as anthracyclines or radiation to the chest area.
• If cardiac dysfunction develops during treatment, dose modification, temporary suspension, or discontinuation of Enhertu may be necessary depending on the severity of the cardiac issues, as discussed in the context of managing cardiac disease in cancer patients 1.

Clinical Guidelines and Recommendations

• The assessment of LV function before the initiation of therapy is recommended by the United States Food and Drug Administration (FDA) for certain therapeutics including trastuzumab and pertuzumab, as mentioned in the ESMO consensus recommendations 1.
• Baseline Doppler echocardiogram (DEcho) is requested to assess cardiac function in patients undergoing therapy with anthracycline, particularly in the presence of CV risk factors, age >60 years, previous CVD, prior mediastinal irradiation, and also in patients undergoing therapy with trastuzumab, especially in those previously treated with anthracycline 1.
• For patients monitored with global longitudinal strain (GLS) evaluations, a baseline assessment is also essential for comparison, highlighting the importance of comprehensive cardiac evaluation before starting potentially cardiotoxic therapies 1.

From the FDA Drug Label

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated

Yes, a cardioechoscopy (echocardiogram) should be performed before initiating treatment with Enhertu (trastuzumab deruxtecan) to assess the left ventricular ejection fraction (LVEF) and identify any potential risk of left ventricular dysfunction 2.

From the Research

Cardiac Monitoring Before Enhertu Treatment

• The decision to perform a cardioechoscopy (echocardiogram) before initiating treatment with Enhertu (trastuzumab deruxtecan) depends on various factors, including the patient's cardiac history and function 3, 4.
• Studies have shown that trastuzumab, a component of Enhertu, can cause cardiotoxicity, leading to a decline in left ventricular ejection fraction (LVEF) 3, 5, 6.
• Early identification of patients at increased risk of trastuzumab-induced myocardial damage is crucial to prevent deterioration to irreversible cardiotoxicity 3.
• The American Society of Echocardiography recommends that patients with a history of cardiovascular disease or those who have received anthracyclines should undergo cardiac monitoring before starting trastuzumab treatment 4.
• A cardioechoscopy can help assess the patient's cardiac function and identify any potential risks associated with Enhertu treatment 4, 7.

Recommendations for Cardiac Monitoring

• Patients with normal cardiac function (LVEF ≥ 53%) can be considered for Enhertu treatment with regular cardiac monitoring 4.
• Patients with impaired cardiac function (LVEF < 53%) should be co-managed by a cardiologist and undergo regular cardiac monitoring 4.
• The frequency and duration of cardiac monitoring should be individualized based on the patient's risk factors and cardiac history 3, 7.
• The use of sensitive and reliable diagnostic techniques, such as 3D-echocardiography and speckle tracking echocardiography, can help identify patients at increased risk of cardiotoxicity 3.