Cardiotoxicity Profiles of Osimertinib Compared with Other EGFR Tyrosine Kinase Inhibitors: A Real-World Comparative Incidence Analysis.

BACKGROUND

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the standard first-line therapy for EGFR-mutant non-small cell lung cancer (NSCLC). Emerging evidence suggests that it may be associated with increased cardiotoxicity; however, current evidence is conflicting, and a small sample size and a lack of direct comparisons with other EGFR-TKIs limit existing studies.

OBJECTIVE

We aim to examine the incidence of cardiovascular toxicity with osimertinib compared with other EGFR-TKIs in a real-world setting.

PATIENTS AND

METHODS

A retrospective cohort study was conducted via the Trinetx global federated health research platform to compare the incidence of cardiotoxicity between osimertinib and other EGFR-TKIs over a 5-year follow-up. Patients were matched using 1:1 propensity score matching (PSM). Outcomes included cardiomyopathies, arrhythmias, ischemic heart disease (IHD), and heart failure (HF), assessed using ICD-10 codes.

RESULTS

Following PSM, each arm consisted of 7331 patients; the arms were well balanced. Osimertinib was associated with increased risk of cardiomyopathy (2.8% vs 0.8%; HR: 3.143 [95% CI 2.342-4.218]), IHD (8.7% vs 5.5%; HR: 1.432 [95% CI 1.248-1.643]), and HF (6.2% vs 4%; HR: 1.41 [95% CI 1.210-1.644]). A similar incidence of arrhythmia was observed (9% vs 8.5%; HR: 0.938 [95% CI 0.831-1.059]); however, it increased after 3 years. Comparisons with individual EGFR-TKIs showed varying results.

CONCLUSION

In this large, real-world study, osimertinib was associated with elevated cardiotoxicity risk. These findings underscore the need for serial monitoring of patients receiving osimertinib and for future studies comparing cardioprotective drugs.