Cardiotoxic Effects of Osimertinib Compared to Other EGFR Inhibitors: A Systematic Review and Meta-Analysis

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) inhibitor, was developed to overcome resistance from EGFR-mutant non-small-cell lung cancer (NSCLC). While it offers significant therapeutic benefits, reports have linked Osimertinib to cardiotoxic effects. This study aims to clarify the direct cardiotoxicity of Osimertinib by reviewing clinical trials and cohort studies involving Osimertinib monotherapy compared to other EGFR inhibitors. A search was conducted in online databases. Measured outcomes included risk of heart failure (HF), myocardial infarction (MI), decline in left ventricular ejection fraction (LVEF), arrhythmias, and pericardial effusion. These outcomes were reported as risk ratio (RR) with a random effects model using 95% confidence intervals (CI). Five studies with 19,008 patients (age 68 ± 13, 65% female) were selected. Osimertinib therapy was associated with an increased risk of HF (RR = 1.45, 95% CI 1.19-1.76, p = 0.0002), decline in LVEF (RR = 3.10, 95% CI 1.72-5.59, p = 0.0002) and MI (RR = 1.40, 95% CI 1.09-1.79, p = 0.0078) compared to other EGFR inhibitors. There was no difference in the risk of arrhythmias and pericardial effusion. Osimertinib therapy is associated with an increased risk of HF and a decline in LVEF compared to other EGFR inhibitors, while associations with MI and arrhythmias were less consistent. Although these events are infrequent, their potential severity warrants proactive cardiac monitoring for patients receiving Osimertinib, particularly in patients with pre-existing risk factors.