Key result
Entrectinib linked to marked symptomatic sinus bradycardia that resolves upon drug discontinuation.
Why the study?
Entrectinib is effective in ROS1 fusion-positive NSCLC and generally well tolerated, but rare and serious cardiac adverse effects have been reported.
Case Report (n=1)
Entrectinib, a targeted kinase inhibitor for NSCLC, can cause profound and symptomatic sinus bradycardia that resolves upon drug discontinuation, highlighting the need for cardio-oncology surveillance.
Symptomatic sinus bradycardia may complicate entrectinib; this case leaves open the incidence and monitoring needs in ROS1+ NSCLC.
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.
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Talasaz et al. (2026) conducted a case report in ROS1-mutant metastatic non-small cell lung cancer (n=1). Entrectinib was evaluated on Symptomatic sinus bradycardia. Entrectinib administration was associated with the development of marked symptomatic sinus bradycardia (38-48 beats/min) which resolved upon discontinuation of the drug.
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