Tyrosine kinase inhibitors and cardiovascular toxicity: a focused review

Tyrosine kinase inhibitors (TKIs) have transformed the treatment of a broad range of hematologic and solid malignancies. However, their expanding use has revealed a spectrum of cardiovascular (CV) toxicities, varying in frequency and severity across drug classes and individual agent. This review summarized the CV adverse effects associated with major classes of small-molecule TKIs including Bruton tyrosine kinase (BTK) inhibitors, vascular endothelial growth factor (VEGF) inhibitors, BCR-ABL inhibitors, epidermal growth factor receptor (EGFR) inhibitors, BRAF/MEK inhibitors, and anaplastic lymphoma kinase (ALK) inhibitors. It also highlights strategies for cardiac surveillance in accordance with the latest cardio-oncology guidelines. BTK inhibitors are associated with atrial fibrillation, hypertension, and bleeding, with hypertension representing a class effect. Newer agents show lower incidence rates of atrial fibrillation. VEGF TKIs are linked to hypertension, left ventricular (LV) dysfunction, and arterial thromboembolic events. BCR-ABL TKIs demonstrate more agent-specific toxicities, including pulmonary arterial hypertension with dasatinib, arterial thromboembolic events, and corrected QT interval (QTc) prolongation with nilotinib and ponatinib. Ponatinib shows dose-dependent toxicity. Imatinib and bosutinib have the most favorable CV safety profiles. Osimertinib, a third-generation EGFR inhibitor, is associated with LV dysfunction. BRAF and MEK inhibitors, especially when used in combination, are associated with hypertension, LV dysfunction, and QTc prolongation. Lorlatinib, an ALK inhibitor, exhibits a distinct cardiometabolic profile, including hyperlipidemia, hypertension, and weight gain. Understanding the class and agent-specific CV risks of TKIs is critical for monitoring and managing CV toxicities effectively. Individualized surveillance and early intervention, guided by the current guideline recommendations, are essential to minimizing CV complications, maintaining continuity of TKI therapies, and improving patient outcomes.