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Cardiotoxicity Profiles of Osimertinib Compared with Other EGFR Tyrosine Kinase Inhibitors: A Real-World Comparative
Zaid Muhanna1, Muntaser Al Zyoud1, Ahmad Issa1
1School of Medicine, University of Jordan, Amman, Jordan.
Background:
Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the standard first-line therapy for EGFR-mutant non-small cell lung cancer (NSCLC). Emerging evidence suggests that it may be associated with increased cardiotoxicity; however, current evidence is conflicting, and a small sample size and a lack of direct comparisons with other EGFR-TKIs limit existing studies.
Objective:
We aim to examine the incidence of cardiovascular toxicity with osimertinib compared with other EGFR-TKIs in a real-world setting.
Patients And Methods:
A retrospective cohort study was conducted via the Trinetx global federated health research platform to compare the incidence of cardiotoxicity between osimertinib and other EGFR-TKIs over a 5-year follow-up. Patients were matched using 1:1 propensity score matching (PSM). Outcomes included cardiomyopathies, arrhythmias, ischemic heart disease (IHD), and heart failure (HF), assessed using ICD-10 codes.
Results:
Following PSM, each arm consisted of 7331 patients; the arms were well balanced. Osimertinib was associated with increased risk of cardiomyopathy (2.8% vs 0.8%; HR: 3.143 [95% CI 2.342-4.218]), IHD (8.7% vs 5.5%; HR: 1.432 [95% CI 1.248-1.643]), and HF (6.2% vs 4%; HR: 1.41 [95% CI 1.210-1.644]). A similar incidence of arrhythmia was observed (9% vs 8.5%; HR: 0.938 [95% CI 0.831-1.059]); however, it increased after 3 years. Comparisons with individual EGFR-TKIs showed varying results.
Conclusion:
In this large, real-world study, osimertinib was associated with elevated cardiotoxicity risk. These findings underscore the need for serial monitoring of patients receiving osimertinib and for future studies comparing cardioprotective drugs.
Insights
Osimertinib, a standard lung cancer drug, is linked to higher risks of heart problems like cardiomyopathy, ischemic heart disease, and heart failure in real-world use. Patients on osimertinib require careful heart monitoring due to these potential cardiovascular toxicities.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Osimertinib is a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC).
- Evidence suggests potential cardiotoxicity with osimertinib, but existing studies have limitations.
- There is a need for real-world data comparing osimertinib's cardiovascular risks with other EGFR-TKIs.
Purpose of the Study:
- To evaluate the incidence of cardiovascular toxicity associated with osimertinib compared to other EGFR-TKIs.
- To assess real-world cardiotoxicity outcomes in NSCLC patients treated with osimertinib versus other EGFR-TKIs.
Main Methods:
- Retrospective cohort study using the Trinetx global federated health research platform.
- Propensity score matching (1:1) was used to compare patients receiving osimertinib and other EGFR-TKIs.
- Cardiovascular outcomes including cardiomyopathies, arrhythmias, ischemic heart disease (IHD), and heart failure (HF) were analyzed over a 5-year follow-up.
Main Results:
- Osimertinib was associated with significantly increased risks of cardiomyopathy (HR: 3.143), IHD (HR: 1.432), and HF (HR: 1.41).
- The incidence of arrhythmia was similar between groups initially but increased after 3 years.
- Comparisons with individual EGFR-TKIs revealed varied results, highlighting drug-specific effects.
Conclusions:
- Osimertinib use is associated with an elevated risk of cardiotoxicity in a real-world setting.
- Routine cardiovascular monitoring is recommended for patients undergoing osimertinib treatment.
- Further research into cardioprotective strategies for patients on osimertinib is warranted.
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