Author + information
- Kartik Anand, MDa,∗ (, )
- Joe Ensor, PhDb,
- Barry Trachtenberg, MDc and
- Eric H. Bernicker, MDa,∗∗ (, )@EricBernicker
- aHouston Methodist Cancer Center/Weill Cornell Medicine, Houston, Texas
- bHouston Methodist Research Institute, Houston, Texas
- cDivision of Cardiology, DeBakey Heart and Vascular Institute, Houston Methodist Hospital, Houston, Texas
- ↵∗Address for correspondence:
Dr. Kartik Anand, Houston Methodist Cancer Center/Weill Cornell Medicine, OPC 24, 6445 Main Street, Houston, Texas 77030.
- ↵∗∗Dr. Eric H. Bernicker, Thoracic and Uveal Melanoma Medical Oncology, Houston Methodist Cancer Center/Weill Cornell Medicine, OPC 24, 6445 Main Street, Houston, Texas 77030.
Objectives The goal of this study was to compare the risk of cardiotoxicity with osimertinib versus all other drugs and versus epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) (erlotinib, afatinib, and gefitinib) in the U.S. Food and Drug Administration Adverse Events Reporting System (FAERS), a pharmacovigilance database.
Background Osimertinib has been shown to improve outcomes in T790M-positive non–small cell lung cancer patients who progress on EGFR-TKI therapy and in the frontline setting in EGFR mutated non–small cell lung cancer. In pivotal trials, osimertinib was associated with higher rates of cardiotoxicity compared with the control arm.
Methods FAERS was queried for “Cardiac failure,” “Electrocardiogram QT-prolonged,” “Atrial Fibrillation (AF),” “Myocardial Infarction (MI),” and “Pericardial Effusion” secondary to “Osimertinib,” “Erlotinib,” “Afatinib,” “Gefitinib,” and all other drugs from 2016 to 2018. Disproportionality signal analysis was performed by calculating the reporting odds ratio (ROR) with its 95% confidence interval (CI). The ROR was considered significant when the lower limit of the 95% CI was >1.0.
Results The ROR (95% CI) for cardiac failure, atrial fibrillation (AF), QT prolongation, myocardial infarction, and pericardial effusion due to osimertinib versus all other drugs in FAERS was 5.4 (4.2 to 7.1), 4.0 (2.8 to 5.8), 11.2 (7.9 to 15.8), 1.6 (0.9 to 2.6), and 8.2 (4.8 to 14), respectively. The ROR (95% CI) for cardiac failure, AF, QT prolongation, myocardial infarction, and pericardial effusion in comparing osimertinib versus other EGFR-TKIs was 2.2 (1.5 to 3.2), 2.1 (1.3 to 3.5), 6.6 (3.4 to 12.8), 1.2 (0.6 to 2.3), and 1.6 (0.8 to 3.3).
Conclusions The RORs for cardiac failure, AF, and QT prolongation were higher due to osimertinib compared with other TKIs. Electrocardiographic monitoring for QT prolongation and monitoring for signs and symptoms of heart failure should be considered in patients taking osimertinib.
Dr. Bernicker serves on the advisory board for Guardant Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This study was presented in part as a poster presentation at the ASCO Annual Meeting, May 31 to June 4, 2019, Chicago, Illinois.
- Received July 12, 2019.
- Revision received October 22, 2019.
- Accepted October 29, 2019.
- 2019 The Authors