Management of Anthracyclines and HER2 Antagonist Cardiotoxicity Anthracyclines cause cardiomyopathy: ✖ Reduction in left ventricular ejection fraction (LVEF) can occur acutely or over years and may or may not be symptomatic. ✖ Incidence rises with increasing doses (7%, 18%, and 65% at cumulative doses of doxorubicin 150 mg/m2, 350 mg/m2, and 550 mg/m2, respectively). HER2 agents cause cardiomyopathy, hypertension, peripheral edema, and arrhythmias: ✖ The risk of cardiomyopathy increases from 4.12 times to 7.19 times higher when used alone vs. sequentially after anthracyclines. Solution: ✔ If cardiomyopathy is detected and treated within 3 months, the reduction in LVEF may be reversible. ✔ Cardiomyopathies attributed to HER2 agents are often reversible with cessation of therapy. ✔ If LVEF drops >10% to below 50%, or 20%, or if heart failure symptoms develop, consider holding therapy (in consultation with oncologist and discussion with the patient) and initiate treatment for heart failure with renin-angiotensin-aldosterone system (RAAS) inhibitor and beta-blocker, mineralocorticoid receptor antagonist (MRA) plus diuretic as needed. ✔ Identify high-risk patients: Age >60 years, baseline cardiac disease (LVEF 50-55% or history of myocardial infarction, moderate to severe valvular disease), ≥2 cardiac risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) ✔ Track cumulative dose, concomitant exposure to radiation and/or trastuzumab Anthracyclines: - Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Mitoxantrone - Monitoring Strategies: • Assess baseline LVEF prior to therapy initiation • LVEF after 4 cycles for all patients • LVEF after each additional cycle beyond doses at which incidence of cardiomyopathy rises • Consider monitoring troponin or global longitudinal strain for early detection of cardiac injury in high risk patients • LVEF 6-12 months after completion of therapy • Long-term monitoring is not well defined - Preventative Strategies: • Identify and treat modifiable risk factors • Anthracycline: Reduce dose, continuous infusion, use of liposomal doxorubicin • Consider dexrazoxane in high-risk patients • Data for prophylactic RAAS inhibitor, beta blocker, or statin in highrisk patients are limited HER2 Inhibitors: - Trastuzumab, Lapatinib, Pertuzumab, Ado-trastuzumab emtansine, Fam-trastuzumab deruxtecan - Monitoring Strategies: • Assess baseline LVEF prior to therapy initiation • LVEF every 3 months during therapy and at completion • LVEF every 6 months for 2 years after completion of trastuzumab • LVEF every 4 weeks if agent held for cardiomyopathy • May resume following recovered LVEF • Permanently discontinue therapy if LVEF does not improve or heart failure develops • Consider global longitudinal strain monitoring to detect patients at higher risk for developing cardiomyopathy - Preventative Strategies: • Identify and treat modifiable risk factors • Data for prophylactic RAAS inhibitor, beta blocker, or statin in highrisk patients are limited #Anthracycline #HER2 #Cardiotoxicity #cardiology #oncology #pharmacology #toxicity #chemotherapy
