Multiple cardiotoxicities during osimertinib therapy

Abstract

Introduction The tyrosine-kinase inhibitor osimertinib is an oral anti-cancer agent that is used for the treatment of patients with metastatic non-small cell lung cancer harbouring sensitising EGFR mutations. Patients receiving osimertinib are at higher risk of developing cardiac toxicity, and here we present the case of a 72-year-old male who developed multiple cardiotoxicities during therapy (i.e. QTc prolongation, atrial fibrillation, heart failure). Case Report A 72-year-old white British, ex-smoker male patient was admitted to our cancer centre with adenocarcinoma of the lung. Afatinib, gefitinib, osimertinib, and carboplatin plus pemetrexed chemotherapy were the treatments he received. At the 15th month of osimertinib therapy, the patient developed QTc prolongation. Two weeks after the first incidence of QTc prolongation, electrocardiography showed rate-controlled atrial fibrillation. In addition to his atrial fibrillation, echocardiography revealed severely impaired left ventricular systolic function (left ventricular ejection fraction: 30%). Management and Outcomes Baseline to osimertinib, an electrocardiography investigation was carried out as per the protocol. Baseline drug history was reviewed and rosuvastatin was discontinued before initiating osimertinib as both drugs contribute to QTc prolongation. Dabigatran, bisoprolol, and digoxin were started for the treatment of atrial fibrillation. Ramipril and spironolactone were prescribed for the treatment of heart failure but osimertinib continued uneventfully. The patient died of non-small cell lung cancer. Discussion Recommendations for practical and clinically relevant baseline and on-treatment assessments are considered which may reduce the risk of cardiac toxicity during osimertinib therapy. These include baseline cardiac risk stratification, consideration of concomitant medications that may result in additive cardiac risk, and use of electrocardiography and echocardiography surveillance.