Cardiotoxicity Quick Reference Guide Reported Anticancer Agents Type of Cardiotoxicity Frequency

Alkylating Agent Cyclophosphamide, Ifosfamide Hemorrhagic Myopericarditis (with high dose) 7-25% Symptomatic Cardiomyopathy 22%

Cisplatin Venous and arterial thromboembolism 12.9% Hypertension 9.4% Hyperlipidemia 7.9% Raynaud Phenomenon 33.4%

Androgen deprivation Metabolic syndrome * therapy/Anti-androgen Aldosterone associated hypertension

Anthracyclines LV dysfunction (dose dependent) 7% @ 150 mg/m2Ŧ (doxorubicin, daunorubicin,

epirubicin, idarubicin, Heart failure (dose dependent) 26% @ 550 mg/m2 Ŧ mitoxantrone)

Checkpoint Inhibitors Myocarditis (rare but potentially fatal) 1% (ipililimumab, nivolumab, Heart failure * pembrolizumab) Arrhythmia *

Chimeric Antigen Receptor Tachycardia 26-57% (CAR) T Cell Therapy Grade 3 or higher 2-4% Arrhythmia 23% Grade 3 or higher 7% Cardiac arrest 4% Cardiac failure 6-7%

Fluropyrimidine Coronary vasospasm 0-19% (5-FU, capecitabine) Myocardial infarction 0-2%

HER-2 targeted therapy LV dysfunction 9.4% (trastuzumab, pertuzumab) with anthracyclines 18.6% Heart failure 0.4-12% with anthracyclines 2-20%

Immunomodulatory agent Venous thromboembolism 0-75% (thalidomide, lenalidomide, Arterial thromboembolism ~5% pomalidomide) Sinus bradycardia (thalidomide) 26% severe or life threatening 3%

PI3K/AKT/mTOR inhibitors Hyperglycemia, hypercholesterolemia, >50% (everolimus, idelasib, hypertriglyceridemia temsirolimus)

Proteasome inhibitors Hypertension 8-23% (bortezomib, carfilzomib) Heart failure (carfilzomib) 4%

Radiation (mediastinal/thoracic) Arrhythmia 16% Autonomic dysfunction 30-45% Coronary heart disease 19-20% Heart failure 11-12% Pacemaker/ICD malfunction 3% Pericardial disease 5% Valvular heart disease 11-31%

Tyrosine kinase inhibitors Arterial thromboembolic event (ponatinib) (see also VSP inhibitors, HER2 Atrial fibrillation (ibrutinib) antagonists and mTOR Atherosclerosis (nilotinib) inhibitors) Bleeding (ibrutinib) Incidence of adverse effects Bradyarrhythmia (trametinib) varies with specific drugs. Edema (imatinib) Hypertension (ibrutinib, trametinib, nilotinb) LV dysfunction (ponatinib, trametinib) QT prolongation (trametinib, dabrafenib, nilotinib) Venous thromboembolic event (ponatinib, erlotinib, trametinib, nilotinib)

VSP Inhibitors Arterial thromboembolic event 0-5.4% (bevacizumab, pazopanib, Hypertension 20-91% sunitinib, sorafenib, axitinib, LV dysfunction 10-15% Venous thromboembolic event 2-11.9%

QT prolongation > 500 ms (vandetanib) 2.7%

Other Cancer Therapies Arsenic trioxide QT prolongation 38%

Decitabine Heart failure, myocardial infarction, <5% supraventricular tachycardia

Docetaxel/paclitaxel Autonomic dysfunction *

Ribociclib QT prolongation 3%

Tretinoin Arrhythmias 23% Heart Failure 6%

Vorinostat QT prolongation 3.2%

* Exact incidence unknown and/or studies conflicting. Ŧ Doxorubicin equivalent dose.