Long QT syndrome after using EGFR-TKIs in older patients with advanced non-small cell lung cancer

Abstract

ABSTRACT Background Long QT syndrome (LQTS) has been reported in older patients with advanced non-small cell lung cancer (NSCLC) following the use of osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). However, there have not been analytic epidemiology studies on this topic. We aimed to compare the risk of LQTS between osimertinib and first/second-generation EGFR-TKIs in older patients with advanced NSCLC. Research design and methods This retrospective observational study used the 2006–2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included older patients with advanced NSCLC who were treated with either osimertinib or first/second-generation EGFR-TKIs during 2007–2017. Inverse probability of treatment weighting (IPTW) was used to balance the two groups with propensity scores estimated based on the patients’ socioeconomic and clinical characteristics. Crude incidence rate (IR) and adjusted hazard ratio (HR) of the primary outcome, incident LQTS, were estimated. Results A total of 545 and 1,135 patients were included in the osimertinib and first/second-generation EGFR-TKI groups, which increased to 1,614 and 1,659, respectively, after IPTW. The osimertinib group had a higher IR of LQTS (2.62 per 100 person-years, 95% CI 2.03–3.38) compared to the first/second-generation EGFR-TKI group (1.33 per 100 person-years, 95% CI 0.92–1.92). After adjusting for covariates, the osimertinib group had a higher risk of LQTS than the first/second-generation EGFR-TKI group, with an HR of 1.94 (95% CI 1.23–3.08). The increased LQTS risk in the osimertinib group was even higher in females, whites and patients aged ≥ 75. Conclusions Given the elevated risk of LQTS associated with osimertinib user, close monitoring for cardiac rhythm irregularities of high-risk patients following initiation of EGFR-TKI is recommended.