The Risk and Reversibility of Osimertinib-Related Cardiotoxicity in a Real-World Population.

Introduction: Although osimertinib, a third-generation EGFR tyrosine kinase inhibitor, as the first-line therapy for metastatic NSCLC was found to have substantial survival benefits, concerns have arisen regarding its potential cardiotoxicity, particularly in real-world clinical settings. We aimed to investigate the incidence, risk factors, and reversibility of osimertinib-related cardiotoxicity.

Methods: We analyzed 1126 patients with NSCLC treated with osimertinib from May 2016 to April 2023 in two cancer centers. Osimertinib-related cardiotoxicity was defined as a composite of osimertinib-related cardiac dysfunction (ORCD), newly developed arrhythmia, and cardiac death. Total follow-up duration was 20.6 (10.8-35.2) months.

Results: The osimertinib was administered for a median of 12.4 months. The incidence of osimertinib-related cardiotoxicity was 4.7%. Advanced age (adjusted hazard ratio with 95% confidence interval: 1.07 [1.04-1.09], p < 0.001), a history of heart failure (3.35 [1.67-9.64], p = 0.025), atrial fibrillation (3.42 [1.27-9.22], p = 0.015), and baseline low left ventricle strain (0.87 [0.79-0.96], p = 0.005) were independently associated with development of cardiotoxicity. The recovery rate of ORCD was 82.4%, which did not differ between patients who discontinued medication and those who did not.

Conclusions: In real-world practice, the incidence of osimertinib-related cardiotoxicity was 4.7%, including 3.4% for ORCD requiring cardiologic intervention, which is higher than previously reported. Given the long-term medication of osimertinib and increased mortality associated with cardiotoxicity, vigilant monitoring is crucial, especially in patients with advanced age, history of heart failure, atrial fibrillation, or decreased baseline left ventricular strain.