Investigation of cardiotoxicity in patients treated with osimertinib: findings from the OSI-FACT study

Introduction: Osimertinib is a highly effective first-line treatment for advanced epithelial growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). With its expanded perioperative use, the long-term risk of cardiotoxicity merits investigation. We assessed the occurrence and risk factors of QT prolongation and cardiac dysfunction in patients with NSCLC treated with first-line osimertinib across multiple institutions. Methods: This retrospective cohort study, a part of the OSI-FACT study, included 538 patients who started first-line osimertinib treatment between August 2018 and December 2019. Patients receiving concurrent anticancer therapies were excluded. Clinical data, including patient characteristics, EGFR mutation status, and tumor stage, were analyzed. Cardiotoxicity graded per Common Terminology Criteria for Adverse Events version 5.0 was monitored via ECG and echocardiography over a median follow-up of 37 months. Results: QT prolongation occurred in 23 patients (4.3 %), with eight reaching Grade ≥3. The median time to onset was 246 days. No significant risk factors for QT prolongation were identified. Cardiac dysfunction was reported in 14 patients (2.6 %), with five cases of Grade ≥3. The median onset was 171 days, with cases occurring after six months. Multivariate analysis identified poor performance status as a risk factor for cardiac dysfunction (HR 2.24, p = 0.005). Conclusion: Osimertinib-related cardiotoxicity, while rare, has important clinical implications, particularly for older patients and those with comorbidities. Regular monitoring, beyond the first year, is essential to ensure patient safety.