Overdrive pacing in the acute management of osimertinib-induced ventricular arrhythmias: A case report and literature review

O simertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), is approved globally as the first-line treatment for patients with EGFR mutations (EGFRm: Ex19del/L858R) and T790M resistance mutations in advanced non-small cell lung cancer (NSCLC). [1−3] With its widespread use, the cardiotoxicity of osimertinib has been of great concern. According to the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS), the main cardiac-related adverse events with EGFR-TKIs are heart failure, QT prolongation, atrial fibrillation, acute myocardial infarction and pericardial effusion, and osimertinib has a higher incidence of QT prolongation, heart failure and atrial fibrillation than other EGFR-TKIs. [4] As mentioned in its package insert, a decline in left ventricular ejection fraction (LVEF) of > 10% from baseline and to less than 50% of LVEF occurred in 3.2% of patients following osimertinib treatment in clinical trials, 0.8% of patients were found to have a heart rate corrected QT interval (QTc) of > 500 ms, and 3.1% of patients had a QTc increase from baseline of > 60 ms. No QTc-related arrhythmias were reported. [5] This is an 81-year-old male patient whose medical history is shown in Figure 1. Eight months ago, two nodules (LU-RADS class 4) in the left upper lung were revealed by CT scan at physical examination, located in the posterior apical segment and the lingual segment (Figure 2A). The patient presented with left-side chest pain and an electrocardiogram suggestive of lateral wall myocardial ischemia (Figure 2B). Accordingly, he underwent coronary angiography, the results of which showed 50% stenosis in the proximal segment of the left anterior descending bra-

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Recurrent ventricular arrhythmias and heart failure induced by osimertinib- a case report

Luo,

Zhou,

Yang

et al. 2024

Front. Cardiovasc. Med.

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BackgroundOsimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor that has become the first-line treatment for non-small cell lung cancer harboring EGFR mutations, with the potential risk of QT prolongation and heart failure. However, few cases have reported malignant ventricular arrhythmias. Here, we report a case of recurrent ventricular fibrillation (VF) and Torsade de Pointes (TdP) secondary to QT prolongation and heart failure induced by osimertinib.Case summaryA 70-year-old woman presented with chest tightness and dyspnea for 1 week and ventricular fibrillation upon admission, with a medical history of lung adenocarcinoma harboring an EGFR exon 21 p.L858R mutation. She was under osimertinib for 3 months. Electrocardiography after defibrillation suggested QTc prolongation (655 ms) and T wave alternans. Ultrasound cardiography displayed left ventricular ejection fraction (LVEF) of 29% and severe mitral regurgitation. Laboratory tests indicated elevated N-terminal pro-B-type natriuretic peptide and hypokalemia. Genetic testing suggested no pathogenic mutations. We considered acquired long QT syndrome and heart failure with reduced ejection fraction induced by osimertinib as the chief causes of ventricular arrhythmia and hypokalemia as an important trigger. Despite intubation, sedation, and the administration intravenous magnesium and potassium and lidocaine, the patient presented with recurrent TdP, which was managed by a low dose of isoproterenol (ISO, 0.17 ug/min). An implantable cardioverter defibrillator was declined. The patient is surviving without any relapse, with QTc of 490 ms and LVEF of 42% after a 6-month follow up.ConclusionRegular monitoring is required during osimertinib administration, considering the risk of life-threatening cardiac events, such as malignant arrhythmias and heart failure. ISO, with an individual dose and target heart rate, may be beneficial for terminating TdP during poor response to other therapies.

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Overdrive pacing in the acute management of osimertinib-induced ventricular arrhythmias: A case report and literature review

Cited by 4 publications

References 21 publications

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Fatal ventricular arrhythmias after osimertinib treatment for lung adenocarcinoma: a case report

Recurrent ventricular arrhythmias and heart failure induced by osimertinib- a case report

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