Sex-specific risk of heart failure and acute myocardial infarction associated with osimertinib in older patients with non-small cell lung cancer

Abstract

Background: The cardiovascular risk associated with the newer epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib, in non-small cell lung cancer (NSCLC) is being reported. While more than half of patients with NSCLC are aged 65 or older, whether the cardiovascular risk increases in older patients treated with osimertinib compared to traditional EGFR-TKIs has not been clearly identified. Objectives: We aimed to identify the risk of major adverse cardiovascular events (MACEs) in older patients treated with osimertinib and traditional EGFR-TKIs, stratifying by sex, age, and race/ethnicity. Design: A retrospective cohort study. Methods: Using the 2006–2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare, older patients with advanced NSCLC prescribed EGFR-TKIs were included. Hazard ratio (HR) and 95% confidence interval (CI) of incident MACEs were calculated using Cox proportional hazard model. Results: Osimertinib had a significantly higher risk of heart failure (HF) [HR, 1.20 (95% CI, 1.01–1.42)] and a lower risk of angina [HR, 0.36 (95% CI, 0.20–0.64)] than first/second-generation EGFR-TKI. The risk of HF and acute myocardial infarction (AMI) was significantly elevated in female [HR, 1.40 (95% CI, 1.13–1.73)] and male [HR, 1.98 (95% CI, 1.13–3.48)] subgroups, respectively, when used osimertinib than first/second-generation EGFR-TKIs. Within osimertinib users, the risk of HF was higher in patients aged ⩾75 ( versus aged 65–74) [HR, 1.71 (95% CI, 1.07–2.71)], White patients ( versus Asian/Pacific Islanders patients) [HR, 1.80 (95% CI, 1.04–3.12)]. The risk of AMI within osimertinib users was higher in White [HR, 3.23 (95% CI, 1.34–7.80)] and Black [HR, 5.63 (95% CI, 1.23–25.87)] than Asian/Pacific Islanders patients. Conclusion: Increased risk of HF was observed in patients who are female, White, and aged ⩾75 while male patients had a higher risk of AMI when treated with osimertinib than first/second-generation EGFR-TKIs. The in-depth examination of osimertinib-induced cardiotoxicity provides evidence for individualized cardiotoxicity surveillance, prevention, and treatment for osimertinib users.