Rationale and design of a cardiac safety study for reduced cardiotoxicity surveillance during HER2-targeted therapy
Anthony F Yu1,2, Chau T Dang3,4, Justine Jorgensen3
1Department of Medicine, Cardiology Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. yua3@mskcc.org.
Background:
Echocardiograms are recommended every 3 months in patients receiving human epidermal growth factor 2 (HER2)-targeted therapy for surveillance of left ventricular ejection fraction (LVEF). Efforts to tailor treatment for HER2-positive breast cancer have led to greater use of non-anthracycline regimens that are associated with lower cardiotoxicity risk, raising into question the need for frequent cardiotoxicity surveillance for these patients. This study seeks to evaluate whether less frequent cardiotoxicity surveillance (every 6 months) is safe for patients receiving a non-anthracycline HER2-targeted treatment regimen.
Methods/Design:
We will enroll 190 women with histologically confirmed HER2-positive breast cancer scheduled to receive a non-anthracycline HER2-targeted treatment regimen for a minimum of 12 months. All participants will undergo echocardiograms before and 6-, 12-, and 18-months after initiation of HER2-targeted treatment. The primary composite outcome is symptomatic heart failure (New York Heart Association class III or IV) or death from cardiovascular causes. Secondary outcomes include: 1) echocardiographic indices of left ventricular systolic function; 2) incidence of cardiotoxicity, defined by a ≥ 10% absolute reduction in left ventricular ejection fraction (LVEF) from baseline to < 53%; and 3) incidence of early interruption of HER2-targeted therapy.
Conclusions:
To our knowledge, this will be the first prospective study of a risk-based approach to cardiotoxicity surveillance. We expect findings from this study will inform the development of updated clinical practice guidelines to improve cardiotoxicity surveillance practices during HER2-positive breast cancer treatment.
Trial Registration:
The trial was registered in the ClinicalTrials.gov registry (identifier NCT03983382) on June 12, 2019.
Insights
This study investigates if 6-month echocardiograms are safe for HER2-positive breast cancer patients on non-anthracycline therapy, potentially reducing cardiotoxicity surveillance frequency. Findings may update clinical guidelines for safer, tailored treatment monitoring.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Current guidelines recommend echocardiograms every 3 months for HER2-targeted therapy patients to monitor left ventricular ejection fraction (LVEF).
- Non-anthracycline HER2-targeted regimens have a lower cardiotoxicity risk, questioning the necessity of frequent surveillance.
- This study evaluates a less frequent surveillance schedule for cardiotoxicity in this patient group.
Purpose of the Study:
- To assess the safety and efficacy of a 6-month echocardiogram surveillance interval for cardiotoxicity.
- To determine if reduced surveillance frequency impacts patient outcomes or treatment continuation.
- To inform potential updates to clinical practice guidelines for HER2-positive breast cancer treatment.
Main Methods:
- Enrollment of 190 women with HER2-positive breast cancer receiving non-anthracycline HER2-targeted therapy for at least 12 months.
- Echocardiograms performed at baseline, and at 6, 12, and 18 months post-treatment initiation.
- Primary outcome: symptomatic heart failure or cardiovascular death. Secondary outcomes: LVEF changes, cardiotoxicity incidence (≥10% LVEF drop to <53%), and treatment interruption.
Main Results:
- This section is not applicable as the study is prospective and results are not yet available in the abstract.
- This section is not applicable as the study is prospective and results are not yet available in the abstract.
- This section is not applicable as the study is prospective and results are not yet available in the abstract.
Conclusions:
- This prospective study pioneers a risk-based approach to cardiotoxicity surveillance in HER2-positive breast cancer patients.
- Expected findings will guide the development of updated clinical practice guidelines.
- The study aims to optimize cardiotoxicity monitoring during HER2-targeted therapy, balancing efficacy and patient safety.
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