학술논문

Osimertinib is associated with reversible and dose-independent cancer therapy-related cardiac dysfunction.
Document Type
Article
Source
Lung Cancer (01695002). Mar2021, Vol. 153, p186-192. 7p.
Subject
*HEART diseases
*NON-small-cell lung carcinoma
*EPIDERMAL growth factor receptors
*CARDIOTOXICITY
*DRUG side effects
*LEFT heart ventricle
*VENTRICULAR ejection fraction
*PROTEIN-tyrosine kinase inhibitors
Language
ISSN
0169-5002
Abstract
• Osimertinib has a higher risk of cardiotoxicities than conventional EGFR-TKIs. • In addition to QTc prolongation, other risks such as decreased LVEF have been noted. • Osimertinib is associated with the risk of reversible and dose-independent CTRCD. • It's not a problem for patients with no history of heart disease and normal LVEF. • Caution should be exercised for patients with moderate-to-severe LVEF reduction. The use of osimertinib is associated with the risk of cancer therapy-related cardiac dysfunction (CTRCD) for EGFR -mutated non–small cell lung cancer (NSCLC) patients. In this study, we aimed to clarify the clinical features of patients with CTRCD associated with osimertinib. A total of 183 cases of advanced EGFR -mutated NSCLC who received osimertinib monotherapy from January 2014 to December 2019 were evaluated. Longitudinal changes in LVEF were evaluated in 58 patients by serial echocardiography before and after osimertinib administration. Of 58 patients, 16 patients (8.7%) had decreased LVEF of 10 units or more and 8 patients (4.4%) met the CTRCD criteria. Overall, LVEF significantly decreased after osimertinib treatment from a mean value of 69% (range, 52-82%) at baseline to 66% (26-75%) (p < 0.001). During osimertinib treatment, LVEF remained low but did not decline any further. Discontinuation, dose reduction, or switching to another EGFR tyrosine kinase inhibitors resulted in recovery in 6 out of 8 CTRCD patients. Multivariate analysis showed that history of heart disease was a significant predictor of CTRCD (ORR, 4.97; 95% confidence interval [CI], 1.26-19.6; P = 0.022). Osimertinib was associated with the risk of CTRCD, which is dose-independent and reversible with drug withdrawal. [ABSTRACT FROM AUTHOR]