Successful Rechallenge with Osimertinib following Osimertinib-Induced Ventricular Tachycardia: A Case Report

• Published in: Case reports in oncology Vol. 16; no. 1; pp. 1100 - 1106
• Main Authors: Saito, Zentaro, Imakita, Takuma, Ito, Takanori, Oi, Issei, Kanai, Osamu, Fujita, Kohei, Tachibana, Hiromasa, Mio, Tadashi
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2023; Karger Publishers
• Subjects: Biopsy; Cancer therapies; Cardiac arrhythmia; Cardiomyocytes; Cardiotoxicity; Case Report; Case reports; Drug dosages; Electrocardiography; Emergency medical care; Heart failure; Heart rate; Kinases; Lung cancer; Medical prognosis; Mutation; osimertinib; Patients; Sinuses; Targeted cancer therapy; Tomography; ventricular tachycardia; United States > US; Osimertinib; Ventricular tachycardia; Cardiotoxicity; Lung cancer
• ISSN: 1662-6575; 1662-6575
• DOI: 10.1159/000533826

Abstract Osimertinib, a third-generation tyrosine kinase inhibitor, is the first-line treatment for metastatic non-small cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor (EGFR) mutations. It is known to cause drug-induced cardiotoxicity, including QT prolongation syndrome, heart failure, and ventricular arrhythmias, which can lead to sudden death. Once severe arrhythmias occur, it is difficult to continue osimertinib treatment. We report a case of a 66-year-old woman with recurrent NSCLC after concurrent chemoradiotherapy who experienced osimertinib-induced ventricular arrhythmia-causing syncope. The patient was initially treated with concurrent chemoradiotherapy, and genetic testing revealed EGFR exon 19 deletion. Three years following treatment initiation, the primary tumor progressed, and new bone metastases developed. The patient was diagnosed with recurrent NSCLC and was treated with targeted therapy with osimertinib. On the 10th day of osimertinib administration, syncope occurred. Electrocardiography showed polymorphic non-sustained ventricular tachycardia, which was believed to be the cause of syncope. The patient was switched to erlotinib. Two and a half years later, disease progression in the primary lesion was observed. A liquid biopsy revealed an EGFR T790M resistance mutation. Therefore, osimertinib (40 mg) was administered every alternate day. After confirming the absence of palpitations and arrhythmias on electrocardiogram, the osimertinib dosing was increased to 40 mg daily. Thereafter, no further events occurred, and tumor shrinkage was observed. Low-dose osimertinib rechallenge after induced ventricular arrhythmia may be considered an option under close monitoring; however, osimertinib rechallenge must be carefully selected based on the risk-benefit analysis.