Entrectinib-induced Brugada phenocopy in a patient with metastatic non-small cell lung cancer

Abstract

Case description A 59-year-old man with metastatic non-small cell lung cancer (NSCLC) was admitted for entrectinib monotherapy, a novel tyrosine kinase inhibitor (TKI), following the discontinuation of crizotinib, which had been administered for 4 months. Entrectinib is efficacious in c-ros oncogene 1 fusion-positive NSCLC. 1 Vasospastic angina had been diagnosed 15 years prior despite no angina after discontinuing oral vasodilators several years earlier. The pre-admission 12-lead electrocardiogram (ECG) findings were within normal limits ( Figure 1A ). Bedside ECG monitoring revealed ST-segment elevation on day 3 after oral entrectinib (600 mg/day) was initiated; the patient was asymptomatic and afebrile. A 12-lead ECG revealed a remarkable ST-segment elevation in the precordial leads, resembling the Brugada Type I pattern ( Figure 1A ). The serum high-sensitivity troponin-I level was slightly elevated (216.4 pg/mL); therefore, an emergency coronary angiography was performed, revealing no occlusion, significant stenosis, or spastic lesions in the coronary arteries ( Figure 1B ). An acetylcholine spasm provocation test induced a coronary spasm ( Figure 1C ), which resolved after administering intra-coronary isosorbide dinitrate ( Figure 1D ). The ST-segment elevation remained unchanged during the investigation ( Figure 1B–D ; see Supplementary material online, Figure S1 ). Left ventricular function and wall thickening were normal on left ventriculography and echocardiography. The entrectinib was discontinued. On day 2 after the discontinuation, the ECG findings normalized ( Figure 1A ) and the serum troponin-I level peaked. Cardiac magnetic resonance imaging revealed no late gadolinium enhancement. Thus, entrectinib-induced Brugada phenocopy was diagnosed. Figure 1 (A) Changes over time in the 12 lead-electrocardiogram findings. Before and 3 days after administering entrectinib and 2 days after discontinuing entrectinib. (B) The initial coronary angiography (upper) and electrocardiogram signal at the V1 lead (lower). (C) Coronary angiography (upper) and electrocardiogram signal at the V1 lead (lower) during the acetylcholine-spasm provocation test. (D) Coronary angiography (upper) and electrocardiogram signal at the V1 lead (lower) after intracoronary administration of isosorbide dinitrate. Brugada phenocopies are Brugada-like ECG patterns induced by reversible clinical conditions. 2 The Brugada phenocopy is rarely associated with anti-cancer drugs. One study 3 reported the Brugada phenocopy in a patient with a pre-existing right bundle branch block following long-term serine/threonine kinase inhibitors administration. However, in our patient, this phenomenon developed rapidly after the administration of a TKI. Unexpected cardiotoxicity and arrhythmogenicity should be monitored when administrating new anti-cancer drugs. Supplementary Material ytad324_Supplementary_Data Click here for additional data file.