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. 2023 Jun 26;12(4):299-304.
doi: 10.1007/s13691-023-00620-y. eCollection 2023 Oct.

Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review

Keisuke Futamura  1 , Tetsunari Hase  1 , Akihito Tanaka  2 , Yoshinori Sakai  3 , Shotaro Okachi  1 , Hirofumi Shibata  1 , Futoshi Ushijima  1 , Takahiko Hashimoto  1 , Kuniya Nakashima  1 , Katsuki Ito  1 , Takanori Yamamoto  3 , Atsushi Numaguchi  3 , Yasuya Inden  2 , Makoto Ishii  1
Affiliations

Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review

Keisuke Futamura et al. Int Cancer Conf J. .

Abstract

Entrectinib, a multikinase inhibitor of ROS1 and tropomyosin receptor kinases, is recommended to treat ROS1-positive metastatic non-small cell lung cancer (NSCLC). In a previous study, entrectinib-related cardiotoxicity occurred in 2% of patients; however, lethal arrhythmias remain understudied. We encountered a case of fatal arrhythmia due to drug-induced Brugada syndrome caused by entrectinib. An 81-year-old Japanese male with lung adenocarcinoma harboring ROS1-fusion gene was treated with entrectinib. The patient developed lethal arrhythmias three days after drug initiation, including ventricular tachycardia with Brugada-like electrocardiogram changes. Echocardiography and coronary angiography revealed no evidence of acute coronary syndrome or myocarditis. Following the termination of entrectinib, the electrocardiogram abnormality improved within 12 days. Hence, paying special attention to and monitoring electrocardiogram changes is necessary. In addition, it is also necessary to consider early therapeutic interventions and discontinuation of the drug in cases of drug-induced Brugada syndrome.

Keywords: Brugada syndrome; Entrectinib; Non-small cell lung cancer; Ventricular tachycardia.

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Conflict of interest statement

Conflict of interestT. Hase received personal fees and research funding from Chugai Pharmaceutical Co. outside the submitted work. All remaining authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Changes in electrocardiogram (ECG). ECGs recorded at baseline a, admission to the intensive care unit b, and 15 h c, three days d, and 12 days e after admission to the intensive care unit. Corrected QT = 0.425 (a), 0.471 (b), 0.391 (c), 0.428 (d), and 0.431 (e). Baseline ECG showed no apparent abnormality (a). At the admission to the intensive care unit, ECG showed ST-segment elevation in V1-V3 and frequent premature ventricular contractions (b). Brugada-like ECG change, manifested by the typical ECG pattern with ST-segment elevations in V1–V2, was gradually apparent (c, d). Twelve days later, the ECG was normalized (e)
Fig. 2
Fig. 2
Electrocardiogram recorded using remote electrocardiographic monitoring at admission to the intensive care unit. A rhythm strip showed ventricular tachycardia
Fig. 3
Fig. 3
Coronary artery angiography. Right a and left b, c coronary angiogram
See this image and copyright information in PMC

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