The third generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as osimertinib, almonertinib, and furmonertinib, played a crucial role in the treatment of advanced non-small cell lung cancer with EGFR gene mutations. However, it was essential to consider their potential cardiotoxicity. Currently, the primary cardiotoxicity associated with this kind of drugs was prolongation of the corrected QT interval, followed by decline in left ventricular ejection fraction and heart failure. These manifestations could occur independently or concurrently. The underlying mechanism responsible for the cardiotoxicity of the third generation EGFR-TKIs remained unknown but might be attributed to inhibition of the human epidermal growth factor receptor 2 (HER-2) signal pathway, suppression of the phosphoinositide 3-kinase (PI3K)/Akt pathway, blockade of the human ether-à-go-go-related gene (hERG) potassium channel, inhibition of the voltage-gated sodium channel (Nav1.5), and modulation of the L-type calcium channel. Therefore, caution should be exercised when using the third generation EGFR-TKIs clinically by promptly identifying high-risk individuals susceptible to cardiotoxicity and closely conducting therapeutic drug monitoring.

Carcinoma, non-small-cell lung; Receptor, epidermal growth factor; Tyrosine kinase inhibitors; Cardiotoxicity; Osimertinib; Almonertinib; Furmonertinib