Supplementary Material for: Successful rechallenge with osimertinib following osimertinib-induced ventricular tachycardia: A case report

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 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 epidermal growth factor receptor (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. An electrocardiogram showed polymorphic non-sustained ventricular tachycardia, thought to be the cause of syncope. The patient was switched to erlotinib. Two and a half years later, disease progression of the primary lesion was observed. Liquid biopsy showed EGFR T790M resistance mutation. Therefore, osimertinib (40 mg) every other day was started. After confirming the absence of palpitations and of arrhythmias on ECG, 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 as an option under close monitoring; however, osimertinib rechallenge must be carefully selected based on the risk-benefit analysis.