Pharmacovigilance Analysis of Cardiac Toxicities Associated With Targeted Therapies for Metastatic NSCLC

被引：50

作者：

Waliany, Sarah ^{[1
]}

Zhu, Han ^{[1
,2
,3
]}

Wakelee, Heather ^{[1
,4
,5
]}

Padda, Sukhmani K. ^{[1
,4
,5
]}

Das, Millie ^{[1
,4
,5
,6
]}

Ramchandran, Kavitha ^{[1
,4
,5
]}

Myall, Nathaniel J. ^{[1
,4
,5
]}

Chen, Thomas ^{[7
]}

Witteles, Ronald M. ^{[1
,2
]}

Neal, Joel W. ^{[1
,4
,5
]}

机构：

[1] Stanford Univ, Dept Med, Sch Med, 875 Blake Wilbur Dr, Stanford, CA 94304 USA

[2] Stanford Univ, Div Cardiovasc Med, Sch Med, Stanford, CA USA

[3] Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA USA

[4] Stanford Univ, Div Oncol, Sch Med, Stanford, CA USA

[5] Stanford Canc Inst, Stanford, CA USA

[6] VA Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA

[7] Stanford Canc Ctr South Bay, Div Oncol, San Jose, CA USA

来源：

JOURNAL OF THORACIC ONCOLOGY | 2021年 / 16卷 / 12期

关键词：

NSCLC; Targeted therapies; Arrhythmia; Heart failure; Cardio-oncology; CELL LUNG-CANCER; OPEN-LABEL; EGFR; ALK; OSIMERTINIB; CRIZOTINIB; CHEMOTHERAPY; ALECTINIB; SURVIVAL; FEATURES;

D O I：

10.1016/j.jtho.2021.07.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Targeted therapies have transformed treatment of driver-mutated metastatic NSCLC. We compared cardiovascular adverse events between and within targeted therapy classes. Methods: We used WHO pharmacovigilance database VigiBase to compare odds of heart failure, conduction disease, QT prolongation, supraventricular tachycardia (SVT), and ventricular arrhythmias between inhibitors of EGFR (erlotinib, gefitinib, afatinib, osimertinib), BRAF (dabrafenib), MEK (trametinib), and ALK and ROS1 (alectinib, brigatinib, ceritinib, crizotinib, lorlatinib). Results: Of 98,765 adverse reactions reported with NSCLC targeted therapies, 1783 (1.8%) were arrhythmias and 1146 (1.2%) were heart failure. ALK and ROS1 inhibitors were associated with increased odds of conduction disease (reporting OR [ROR] = 12.95, 99% confidence interval [CI]: 10.14-16.55) and QT prolongation (ROR = 5.16, 99% CI: 3.92-6.81) relative to BRAF and EGFR inhibitors. Among ALK and ROS1 inhibitors, crizotinib had highest odds of conduction disease (ROR = 1.75, 99% CI: 1.30-2.36) and QT prolongation (ROR = 1.91, 99% CI: 1.22-3.00). Dabrafenib (ROR = 2.24, 99% CI: 1.86-2.70) and trametinib (ROR = 2.44, 99% CI: 2.03-2.92) had higher odds of heart failure than other targeted therapies. Osimertinib was strongly associated with QT prolongation (ROR = 6.13, 99% CI: 4.43-8.48), heart failure (ROR = 3.64, 99% CI: 2.94- 4.50), and SVT (ROR = 1.90, 99% CI: 1.26-2.86) relative to other targeted therapies. Conclusions: ALK and ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than other targeted therapies. Osimertinib is strongly associated with QT prolongation, SVT, and heart failure relative to other EGFR inhibitors and targeted therapies. Monitoring for heart failure and arrhythmias should be considered with NSCLC targeted therapies, especially osimertinib.

引用

页码：2029 / 2039

页数：11

共 38 条

[11] EGFR-TKIs plus bevacizumab demonstrated survival benefit than EGFR-TKIs alone in patients with EGFR-mutant NSCLC and multiple brain metastases [J].