Unmasking the Heart of Osimertinib: A Closer Look at Drug-Induced Cardiotoxicity

BACKGROUND: Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is an effective therapy for epidermal growth factor receptor-mutated non-small cell lung cancer, but it has been associated with a higher incidence of cardiotoxicity. CASE SUMMARY: A 91-year-old woman on osimertinib 80 mg daily presented with acute dyspnea and was found to have a newly reduced left ventricular ejection fraction of 30%. Coronary angiography excluded obstructive coronary disease. Osimertinib was discontinued, and guideline-directed medical therapy (GDMT) was initiated, resulting in left ventricular ejection fraction recovery to 60%. The patient was successfully rechallenged with osimertinib while continuing GDMT, without recurrence of cardiomyopathy. DISCUSSION: Although rare, osimertinib-induced cardiotoxicity may manifest as heart failure, arrhythmias, or QT interval prolongation. TAKE-HOME MESSAGES: This case underscores the potential of GDMT not only for recovery, but also for safe continuation of osimertinib. Prophylactic use of GDMT before initiating osimertinib may help reduce the risk of future cardiotoxic events.