AUTHOR=Le Jonathan N. , Gasho Jordan O. , Peony Olivia , Singh Asneh , Silos Katrina D. , Kim Sungjin , Nguyen Anthony T. , Kamrava Mitchell , Mirhadi Amin , Hakimian Behrooz , Reckamp Karen L. , Sankar Kamya , Mak Raymond H. , Nikolova Andriana P. , Atkins Katelyn M. 

TITLE=Cardiac events and dynamic echocardiographic and electrocardiogram changes following osimertinib treatment in lung cancer

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 11 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2024.1485033

DOI=10.3389/fcvm.2024.1485033

ISSN=2297-055X

ABSTRACT=Osimertinib is first-line treatment for epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC) and has been associated with cardiotoxicity. However, the nature of cardiac remodeling and associated risk factors remains incompletely understood. Retrospective analysis of NSCLC patients with ≥1 echocardiogram post-osimertinib between 2007 and 2022 was performed. The cumulative incidence of grade ≥2 cardiac common terminology criteria for adverse events (CTCAE) was estimated and Fine and Gray regressions performed (non-cardiac death as competing risk). Eighty-five patients [mean [interquartile range, IQR], 68 [60–75] years; 67% female; 12% with pre-existing heart conditions] met inclusion criteria. With a median follow up of 34.7 months, the 2-year cumulative incidence of grade ≥2 and grade ≥3 cardiac events were 19.2% and 8.5%, respectively. There was an increased risk of grade ≥2 cardiac CTCAE with pre-existing arrhythmia [hazard ratio(HR) 3.90, 95%CI, 1.11–13.72; p = 0.034] and higher body mass index (HR 1.07, 95%CI, 1.00–1.14; p = 0.04). Following osimertinib (vs. baseline), the median QTc was prolonged (451 vs. 437 ms; p < 0.001) and LVEF ≤50% was more common (10.6% vs. 5.3%; p = .046). Osimertinib treatment was associated with QTc prolongation and reduced LVEF. BMI was identified as a potentially modifiable risk factor for osimertinib-associated cardiotoxicity, worthy of further study.