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Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique
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Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique

Published on: November 11, 2022

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ALK inhibitor-induced bradycardia: A systematic-review and meta-analysis

Filipe Cirne1, Shijie Zhou1, Coralea Kappel1

  • 1Department of Medicine, McMaster University and Hamilton Health Sciences, Hamilton, Canada.

Lung Cancer (Amsterdam, Netherlands)
|September 7, 2021
PubMed
Abstract

Insights

Anaplastic Lymphoma Kinase (ALK) inhibitors improve outcomes in advanced non-small cell lung cancer (NSCLC). Crizotinib increases bradycardia risk versus chemotherapy, but newer ALK inhibitors show similar risks to crizotinib.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Anaplastic Lymphoma Kinase (ALK) inhibitors have transformed advanced ALK-positive non-small cell lung cancer (NSCLC) treatment.
  • Bradycardia is a known adverse effect of ALK inhibitors.

Purpose of the Study:

  • To determine the risk of bradycardia associated with ALK inhibitors in advanced NSCLC patients.
  • To compare bradycardia incidence between different ALK inhibitors and standard chemotherapy.

Main Methods:

  • Systematic literature search of major databases (MEDLINE, EMBASE, etc.).
  • Inclusion of randomized controlled trials comparing ALK inhibitors to other ALK inhibitors or chemotherapy.
  • Meta-analysis to pool incidence rates of bradycardia and dizziness.

Main Results:

  • Pooled incidence of bradycardia was 8% among 1737 patients on ALK inhibitors.
  • Crizotinib showed a significantly higher risk of bradycardia than standard chemotherapy (RR 24.68).
  • No significant difference in bradycardia risk was observed between crizotinib and newer ALK inhibitors (alectinib, brigatinib, lorlatinib). Dizziness was more frequent with ALK inhibitors than chemotherapy (RR 1.88).

Conclusions:

  • Crizotinib is associated with a higher risk of bradycardia compared to standard chemotherapy in NSCLC.
  • Newer generation ALK inhibitors do not appear to have a higher bradycardia risk than crizotinib.
Keywords:
ALK inhibitorsBradycardiaCardio-oncologyDizzinessMeta-analysisNon-small cell lung cancer

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