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.

奥希替尼（Osimertinib）作为第三代酪氨酸激酶抑制剂，是伴致敏性表皮生长因子受体（epidermal growth factor receptor, EGFR）突变的转移性非小细胞肺癌（non-small cell lung cancer, NSCLC）的一线治疗方案。已知其可引发药物性心脏毒性，包括QT间期延长综合征、心力衰竭及室性心律失常，严重者可导致猝死。一旦发生严重室性心律失常，奥希替尼的临床应用通常难以继续。本文报告1例66岁女性患者：该患者在接受同步放化疗后出现复发性非小细胞肺癌，后因使用奥希替尼引发室性心律失常导致晕厥。患者初始接受同步放化疗，基因检测提示表皮生长因子受体19外显子缺失。治疗启动3年后，原发肿瘤进展并出现新发骨转移，确诊为复发性非小细胞肺癌，遂予奥希替尼靶向治疗。用药第10天时，患者突发晕厥，心电图检查示多形性非持续性室性心动过速，考虑为晕厥的诱因。随后患者换用厄洛替尼（erlotinib）。2.5年后，患者原发灶出现疾病进展，液体活检检出EGFR T790M耐药突变，故予隔日口服40mg奥希替尼。在确认患者无心悸症状、心电图无心律失常表现后，将奥希替尼剂量调整为每日40mg。此后未再发生不良事件，且观察到肿瘤缩小。综上，在严密监测下，可考虑对出现药物诱导室性心律失常的患者采用低剂量奥希替尼再挑战治疗，但需基于风险获益分析谨慎选择该方案。