HER2HEART-US: Primary Prevention of Cardiotoxicity in Breast Cancer Patients Receiving HER2-directed Therapy: a Pilot 2x2 Factorial Randomized Controlled Trial
Ten to 15% of patients with breast cancer are HER2 positive, with treatment focused on targeting the HER2 receptor. Although these treatments are generally well tolerated, they are associated with an increased risk of cardiomyopathy. There are currently no treatments proven to prevent the cardiotoxicities associated with HER2-targeted therapy, but there is convincing preclinical data demonstrating that prophylactic treatment with a beta blocker (BB) and/or an SGLT2 inhibitor (SGLT2i) may each independently prevent cardiotoxicity and HER-targeted treatment interruptions. The proposed pilot study will assess the feasibility and preliminary efficacy and safety of therapy with both a beta blocker (carvedilol) and an SGLT2 inhibitor (empagliflozin), alone and in combination, in a population initiating HER2-directed therapy for HER2+ breast cancer. The hypotheses being tested in this study are: 1. It is feasible to recruit 20-40 patients over 6 months 2. There are no differences in tolerability and safety between participants taking carvedilol and/or empagliflozin and those receiving usual care.
• Histologically or cytologically confirmed HER2+ breast cancer by ASCO/CAP guidelines of any clinical or pathologic stage.
• Planning to commence standard of care HER2-directed therapy or started HER2-directed therapy within 6 months prior to randomization
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• For patients newly commencing HER2-directed therapy, left ventricular ejection fraction (LVEF) ≥ 50% up to 30 days prior to enrollment detected by echocardiogram. For patients already receiving HER2-directed therapy, LVEF ≥ 50% after the last cycle of therapy prior to enrollment. (Patient will be enrolled at the time of their next cycle after the echocardiogram.)
• Systolic blood pressure ≥ 100 mmHg and resting heart rate ≥ 60 bpm.
• eGFR \> 30 mL/min/1.73m\^2.
• Women of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Patients with an acceptable support system (as determined by the treating medical team).
• Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.