LUNG CANCER: Real-world data suggests osimertinib is associated with a 5% risk of cardiac adverse events. This drug has previously been linked to QT prolongation, cardiomyopathy and heart failure.

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March 30, 2020

SCIENTIFIC

Cardiac Adverse Events in EGFR-Mutated Non-Small Cell Lung Cancer Treated With Osimertinib

JACC JOURNAL, March 1st 2020

Abstract

Objectives

The purpose of this study was to assess osimertinib-associated cardiac adverse events (AEs) in a real-world setting, using a retrospective single-center cohort study in Japan. Background Cases of osimertinib-associated cardiac AEs have been reported but remain poorly understood.

Methods

A total of 123 cases of advanced non–small cell lung cancer (NSCLC) with confirmed EGFR mutations who received osimertinib monotherapy from 2014 to 2019 at the Osaka International Cancer Institute (Osaka, Japan) were evaluated. Cardiac AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Changes in left ventricular ejection fraction (LVEF) and rates of cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a ≥10 % absolute decline in LVEF from baseline to a value of <53%, were further assessed in 36 patients in whom serial measurements of LVEF were obtained before and during osimertinib treatment.

Results

Severe cardiac AEs (CTCAE grade 3 or higher) occurred in 6 patients (4.9%) after osimertinib administration. These AEs included acute myocardial infarction (n = 1), heart failure with reduced LVEF (n = 3), and valvular heart disease (n = 2). Five of the 6 patients had a history of cardiovascular risk factors or disease. Myocardial biopsies in 2 of the patients showed cardiomyocyte hypertrophy and lipofuscin deposition. In 36 patients assessed with serial LVEF, LVEF declined from 69.4 ± 4.2% to 63.4 ± 10.5% with osimertinib therapy (p < 0.001). CTRCD occurred in 4 patients with a nadir LVEF of 40.3 ± 9.1% with osimertinib.

Conclusions

In this retrospective cohort analysis, the incidence of cardiac AEs in patients treated with osimertinib was 4.9%. Additional prospective data collected from patients with NSCLC treated with osimertinib will be important in understanding the incidence, pathophysiology, and management of cardiac AEs with osimertinib.

https://cardiooncology.onlinejacc.org/content/2/1/1