Cardiotoxic Effects of Osimertinib Compared to Other EGFR Inhibitors: A Systematic Review and Meta-Analysis
Alan Garcia1, Abdul Mueez Alam Kayani2, Daniel Alejandro Navarro-Martinez3
1Department of Internal Medicine, Indiana University School of Medicine, 340 West 10th Street Fairbanks Hall, Suite 6200, Indianapolis, IN, 46202-3082, USA. alangarc@iu.edu.
Abstract:
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) inhibitor, was developed to overcome resistance from EGFR-mutant non-small-cell lung cancer (NSCLC). While it offers significant therapeutic benefits, reports have linked Osimertinib to cardiotoxic effects. This study aims to clarify the direct cardiotoxicity of Osimertinib by reviewing clinical trials and cohort studies involving Osimertinib monotherapy compared to other EGFR inhibitors. A search was conducted in online databases. Measured outcomes included risk of heart failure (HF), myocardial infarction (MI), decline in left ventricular ejection fraction (LVEF), arrhythmias, and pericardial effusion. These outcomes were reported as risk ratio (RR) with a random effects model using 95% confidence intervals (CI). Five studies with 19,008 patients (age 68 ± 13, 65% female) were selected. Osimertinib therapy was associated with an increased risk of HF (RR = 1.45, 95% CI 1.19-1.76, p = 0.0002), decline in LVEF (RR = 3.10, 95% CI 1.72-5.59, p = 0.0002) and MI (RR = 1.40, 95% CI 1.09-1.79, p = 0.0078) compared to other EGFR inhibitors. There was no difference in the risk of arrhythmias and pericardial effusion. Osimertinib therapy is associated with an increased risk of HF and a decline in LVEF compared to other EGFR inhibitors, while associations with MI and arrhythmias were less consistent. Although these events are infrequent, their potential severity warrants proactive cardiac monitoring for patients receiving Osimertinib, particularly in patients with pre-existing risk factors.
Insights
Osimertinib (a third-generation epidermal growth factor receptor inhibitor) increases the risk of heart failure and reduced ejection fraction in non-small-cell lung cancer patients. Proactive cardiac monitoring is recommended due to potential cardiotoxicity.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Osimertinib is a third-generation epidermal growth factor receptor (EGFR) inhibitor used for EGFR-mutant non-small-cell lung cancer (NSCLC).
- Previous reports suggest Osimertinib may cause cardiotoxic effects, necessitating further investigation.
- Understanding Osimertinib's direct cardiotoxicity is crucial for patient safety and treatment management.
Purpose of the Study:
- To evaluate the direct cardiotoxicity of Osimertinib compared to other EGFR inhibitors.
- To assess the risk of specific cardiac adverse events associated with Osimertinib monotherapy.
Main Methods:
- A systematic review and meta-analysis of clinical trials and cohort studies.
- Inclusion criteria focused on Osimertinib monotherapy versus other EGFR inhibitors.
- Outcomes included heart failure (HF), myocardial infarction (MI), left ventricular ejection fraction (LVEF) decline, arrhythmias, and pericardial effusion, analyzed using risk ratios (RR) and 95% confidence intervals (CI).
Main Results:
- Osimertinib therapy was linked to a significantly increased risk of HF (RR=1.45) and decline in LVEF (RR=3.10) compared to other EGFR inhibitors.
- An increased risk of MI (RR=1.40) was also observed with Osimertinib.
- No significant differences were found in the risk of arrhythmias or pericardial effusion.
Conclusions:
- Osimertinib therapy is associated with a higher incidence of heart failure and reduced left ventricular ejection fraction.
- While associations with myocardial infarction and arrhythmias were less consistent, potential cardiotoxicity warrants attention.
- Proactive cardiac monitoring is advised for patients on Osimertinib, especially those with pre-existing cardiac risk factors.
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