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Long QT syndrome after using EGFR-TKIs in older patients with advanced non-small cell lung cancer
Joo-Young Byun1,2, Sola Han1, Aiham Qdaisat3
1Health Outcomes division, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
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.
Insights
Osimertinib, a third-generation EGFR-TKI, is linked to a higher risk of Long QT syndrome (LQTS) in older patients with advanced non-small cell lung cancer compared to earlier generations. Close cardiac monitoring is advised for high-risk individuals.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Long QT syndrome (LQTS) is a known risk in older patients with advanced non-small cell lung cancer (NSCLC) treated with osimertinib.
- Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI).
- Analytic epidemiological studies comparing LQTS risk between osimertinib and earlier EGFR-TKIs are lacking.
Purpose of the Study:
- To compare the risk of LQTS between osimertinib and first/second-generation EGFR-TKIs.
- To investigate LQTS incidence in older patients with advanced NSCLC receiving different EGFR-TKIs.
Main Methods:
- Retrospective observational study using SEER-Medicare data (2006-2019).
- Included older patients with advanced NSCLC treated with osimertinib or first/second-generation EGFR-TKIs (2007-2017).
- Inverse probability of treatment weighting (IPTW) used for balancing covariates; incidence rates (IR) and hazard ratios (HR) calculated.
Main Results:
- Osimertinib group (n=1,614 post-IPTW) showed a higher LQTS incidence rate (2.62 per 100 person-years) than the first/second-generation EGFR-TKI group (n=1,659; 1.33 per 100 person-years).
- Osimertinib use was associated with a significantly higher risk of LQTS (HR=1.94; 95% CI 1.23-3.08).
- Elevated LQTS risk with osimertinib was more pronounced in females, white patients, and those aged ≥75.
Conclusions:
- Osimertinib use is associated with an increased risk of LQTS in older patients with advanced NSCLC.
- Close monitoring for cardiac rhythm irregularities is recommended for high-risk patients initiating EGFR-TKI therapy.
- Further research may explore mechanisms and specific risk factors for osimertinib-induced LQTS.
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