Entrectinib-Induced Sinus Bradycardia in a Patient With Metastatic Non-Small Cell Lung Cancer.

BACKGROUND

Targeted therapies like tyrosine kinase inhibitors have significantly improved outcomes in non-small cell lung cancer. Entrectinib, a multikinase inhibitor, showed efficacy in ROS1 fusion-positive NSCLC, including intracranial metastases. Although generally well tolerated, rare but serious cardiac adverse effects have been reported.

CASE SUMMARY: We report a 51-year-old woman with ROS1-mutant metastatic non-small cell lung cancer who developed symptomatic sinus bradycardia during entrectinib therapy. After disease progression on crizotinib, lorlatinib, and reprotrectinib, she was started on entrectinib. Within 1 week, she developed marked bradycardia (38-48 beats/min) with lightheadedness. Electrocardiogram and echocardiography confirmed sinus bradycardia with mildly reduced ejection fraction. Entrectinib was discontinued, and symptoms resolved with heart rate normalization.

TAKE-HOME MESSAGES: Sinus bradycardia may be a rare but significant side effect of entrectinib, possibly related to ALK inhibition. Cardiac monitoring and multidisciplinary management are essential when initiating therapy with ALK/ROS1 inhibitors.