Osimertinib linked to more therapy-related cardiac events than other TKIs for NSCLC
Key takeaways:
- Patients with EGFR-mutated NSCLC who received osimertinib had an elevated risk for therapy-related cardiac events.
- Cardiac events were independently associated with survival.
Patients with EGFR-mutated non-small cell lung cancer treated with osimertinib experienced more cancer therapy-related cardiac events than those treated with other EGFR tyrosine kinase inhibitors.
“Despite the extended survival observed in patients with EGFR variations treated with osimertinib compared with gefitinib [Iressa, AstraZeneca] or erlotinib, long-term outcomes may be compromised by significant cardiac risks — particularly given the high prevalence of EGFR variants (about 50%) in Asian populations,” Chien-Yu Lin, MD, attending physician in the department of internal medicine at National Cheng Kung University Hospital in Taiwan, and colleagues wrote.
“A retrospective study involving a Japanese population reported grade 3 or higher cardiac adverse events in nearly 5% of patients, a rate higher than that observed in clinical trials,” researchers added. “The present study revealed an even higher incidence of cardiovascular toxic effects at 14.9% — including newly emerging arrhythmias, valvular heart diseases, myocardial infarction and heart failure. [This aligns] with a case series that showed a more severe clinical phenotype in the osimertinib group than previously recognized.”
Prior studies demonstrated osimertinib mesylate (Tagrisso, AstraZeneca) can extend survival compared with first- or second-generation EGFR TKIs.
Lin and colleagues conducted a cohort study to compare cancer therapy-related cardiac events (CTRCEs) based on type of therapy patients with EGFR-mutated NSCLC received.
CTRCEs included newly emerging arrhythmias, valvular heart diseases (moderate and more), myocardial infarction and heart failure. Investigators adjusted analyses to account for age, sex, smoking, alcohol consumption, BMI, cardiovascular comorbidities, thoracic radiotherapy and cardiovascular medications.
Researchers also compared OS with osimertinib vs. other EGFR TKIs.
Due to the high prevalence of EGFR variants among Asian populations, researchers conducted the cohort study at National Cheng Kung University Hospital in Taiwan.
The cohort included 401 patients (63.1% women; mean age, 69.2 years) who began treatment between September 2019 and July 2022.
A comparable percentage of patients received osimertinib (48.6%) or other EGFR TKIs (51.4%).
After median follow-up of 23.2 months, results showed a significantly higher rate of CTRCEs in the osimertinib group (14.9% vs. 4.4%; HR = 3.37; 95% CI, 1.56-7.26).
This finding persisted in analyses adjusted for relevant cardiovascular risk factors (adjusted subdistribution HR = 4; 95% CI, 1.81-8.85).
CTRCEs also appeared independently associated with OS (HR = 4.02; 95% CI, 2.44-6.63).
Researchers acknowledged study limitations, including its retrospective nature and a lack of data on the effect osimertinib-induced cardiac toxic events had on patients’ quality of life. Also, because of the timing of treatment initiation, not all patients received routine echocardiography as recommended in European Society of Cardiology guidelines issued in 2022.
“These findings highlight the importance of cardiac monitoring to evaluate cardiovascular toxic effects in these patients, irrespective of preexisting cardiac risk factors,” researchers wrote.
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