Entrectinib-Induced Myocarditis and Acute Heart Failure Responding to Steroid Treatment: A Case Report

A 72-year-old man presented to his general practitioner with worsening dyspnea and was diagnosed with having recurrent <i>ROS1</i>-positive stage IIIB NSCLC 8 years after initial diagnosis and radical treatment for early stage disease. He was subsequently started on entrectinib but required hospital admissions for recurrent acute kidney injuries on a background of chronic kidney disease. His entrectinib was withheld on day 20 since his first dose of treatment while he was being investigated. Nevertheless, he continued to experience worsening dyspnea and bilateral pedal edema and later developed acute pulmonary edema 31 days after his first dose of entrectinib, despite the drug being withheld for the past 11 days. Results of biochemical tests and cardiac imaging confirmed acute myocarditis. Initially, he was treated with standard heart failure medications without clinical improvement or decline in N-terminal pro B-type natriuretic peptide levels. Nevertheless, he noticed significant improvement after starting a short course of prednisolone, which led to complete resolution of symptoms, improved N-terminal pro B-type natriuretic peptide levels, and recovery of left ventricular ejection fraction. His treatment was subsequently changed to crizotinib, which was well tolerated. This is the third reported case of entrectinib-induced myocarditis and the first reported case which has been successfully managed with steroid therapy. This case was also associated with concurrent acute heart failure after entrectinib treatment which responded promptly to prednisolone (40 mg). Entrectinib-induced cardiotoxicity is an important adverse event to be aware of, particularly as patients may be asymptomatic for an initial period before significant deterioration.