Core Insights - Lung cancer is the leading cancer globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. EGFR mutations are present in 40-50% of East Asian patients and 10-20% of Caucasian patients [2] - EGFR tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis and quality of life for patients with EGFR-mutated NSCLC, with third-generation EGFR TKIs now considered the standard first-line treatment for advanced cases [2] - Despite the benefits, EGFR TKIs are associated with cardiovascular adverse events, which can lead to treatment interruptions or discontinuations. However, systematic evaluations of their cardiovascular impacts have been lacking [2][3] Study Overview - A recent study published in The BMJ analyzed cardiovascular risks associated with different generations of EGFR TKIs in EGFR-mutated NSCLC patients. This research marks a significant achievement for the First Affiliated Hospital of Henan University of Medicine [3][4] Key Findings - The study found that both first and third-generation EGFR TKIs, as well as their combinations with anti-angiogenic drugs, are linked to increased cardiovascular adverse events. The risk associated with third-generation EGFR TKIs is significantly higher than that of first-generation [4] - A network meta-analysis included 89 randomized controlled trials with 29,813 participants, revealing that third-generation EGFR TKIs are associated with a 118% increase in cardiac adverse events compared to placebo, while first-generation EGFR TKIs are linked to a 51% increase [6] - Specific third-generation EGFR TKIs, such as Osimertinib and Lazertinib, showed particularly high cardiac toxicity, with risks increasing by 153% and 184%, respectively. Different third-generation EGFR TKIs exhibit varying toxicity profiles, necessitating individualized treatment choices [6] Combination Therapy Risks - The study highlighted a "cumulative effect" of cardiovascular risks when EGFR TKIs are combined with other drugs. The combination of first-generation EGFR TKIs with anti-angiogenic drugs primarily increases vascular adverse reactions, while third-generation EGFR TKIs combined with anti-angiogenic therapies increase both cardiac and vascular adverse reactions [8] Clinical Implications - For patients with pre-existing heart conditions, careful drug selection is crucial. It may be advisable to avoid high-risk third-generation EGFR TKIs or their combination with anti-angiogenic drugs [10] - Enhanced cardiovascular monitoring is recommended for patients requiring potent treatments, especially if high-risk regimens are necessary. Personalized treatment decisions are essential to balance expected efficacy and potential cardiovascular risks [11] Conclusion - This research provides valuable evidence for clinical guidelines regarding the cardiovascular toxicity of EGFR TKIs, emphasizing the need to balance treatment efficacy with cardiovascular risks. Continuous monitoring and assessment of safety for new EGFR TKIs are critical as they are developed and applied [12]