PMID- 34396203
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240403
IS  - 2666-0873 (Electronic)
IS  - 2666-0873 (Linking)
VI  - 2
IP  - 1
DP  - 2020 Mar
TI  - Cardiac Adverse Events in EGFR-Mutated Non-Small Cell Lung Cancer Treated 
      With Osimertinib.
PG  - 1-10
LID - 10.1016/j.jaccao.2020.02.003 [doi]
AB  - 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.
CI  - (c) 2020 The Authors.
FAU - Kunimasa, Kei
AU  - Kunimasa K
AD  - Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Kamada, Risa
AU  - Kamada R
AD  - Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Oka, Toru
AU  - Oka T
AD  - Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Oboshi, Makiko
AU  - Oboshi M
AD  - Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Kimura, Madoka
AU  - Kimura M
AD  - Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Inoue, Takako
AU  - Inoue T
AD  - Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Tamiya, Motohiro
AU  - Tamiya M
AD  - Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Nishikawa, Tatsuya
AU  - Nishikawa T
AD  - Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Yasui, Taku
AU  - Yasui T
AD  - Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Shioyama, Wataru
AU  - Shioyama W
AD  - Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Nishino, Kazumi
AU  - Nishino K
AD  - Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Imamura, Fumio
AU  - Imamura F
AD  - Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Kumagai, Toru
AU  - Kumagai T
AD  - Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Fujita, Masashi
AU  - Fujita M
AD  - Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20200317
PL  - United States
TA  - JACC CardioOncol
JT  - JACC. CardioOncology
JID - 101761697
PMC - PMC8352275
OTO - NOTNLM
OT  - ACE, angiotensin-converting enzyme
OT  - AE, adverse event
OT  - ARB, angiotensin II receptor blocker
OT  - CTCAE, common terminology criteria for adverse event
OT  - CTRCD, cancer therapeutics-related cardiac dysfunction
OT  - EGFR mutations
OT  - EGRF, epidermal growth factor receptor
OT  - HER, human epidermal growth factor receptor
OT  - LVEF, left ventricular ejection fraction
OT  - LVIDd, left ventricular internal end-diastolic diameter
OT  - LVIDs, left ventricular internal end-systolic diameter
OT  - MR, mitral regurgitation
OT  - NSCLC, non-small cell lung cancer
OT  - NT-proBNP, N-terminal pro-B-type natriuretic peptide
OT  - PASP, pulmonary artery systolic pressure
OT  - TKI, tyrosine kinase inhibitor
OT  - TR, tricuspid regurgitation
OT  - VEGF, vascular endothelial growth factor
OT  - cardiac adverse events
OT  - cardiac dysfunction
OT  - myocardial biopsy
OT  - non-small cell lung cancer
OT  - osimertinib
EDAT- 2020/03/17 00:00
MHDA- 2020/03/17 00:01
PMCR- 2020/03/17
CRDT- 2021/08/16 06:10
PHST- 2019/08/28 00:00 [received]
PHST- 2020/01/31 00:00 [revised]
PHST- 2020/02/03 00:00 [accepted]
PHST- 2021/08/16 06:10 [entrez]
PHST- 2020/03/17 00:00 [pubmed]
PHST- 2020/03/17 00:01 [medline]
PHST- 2020/03/17 00:00 [pmc-release]
AID - S2666-0873(20)30010-7 [pii]
AID - 10.1016/j.jaccao.2020.02.003 [doi]
PST - epublish
SO  - JACC CardioOncol. 2020 Mar 17;2(1):1-10. doi: 10.1016/j.jaccao.2020.02.003. 
      eCollection 2020 Mar.