Frontiers in Cardiovascular Medicine (Dec 2024)

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

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

DOI
https://doi.org/10.3389/fcvm.2024.1485033
Journal volume & issue
Vol. 11

Abstract

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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.

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