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ALK inhibitor-induced bradycardia: A systematic-review and meta-analysis
- Source :
- Lung Cancer. 161:9-17
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Introduction Anaplastic Lymphoma Kinase (ALK) inhibitors have revolutionized the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC), improving progression-free survival. Bradycardia is a potential adverse effect of these agents. We aimed to determine the risk of bradycardia associated with ALK inhibitors in patients with advanced NSCLC. Materials and methods We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, National clinical trial registry, and Web of Science Core Collection. We included all randomized controlled trials in which an ALK-inhibitor was compared with another ALK-inhibitor or standard chemotherapy. Meta-analyses were conducted to evaluate the pooled incidence rates of bradycardia and dizziness using fixed effect models. Results The pooled incidence of bradycardia among 1737 individuals prescribed ALK inhibitors was 8% during a mean follow-up of 1.26 years. Crizotinib led to more bradycardia than standard chemotherapy (relative risk, RR 24.68, 95% CI 7.11–85.), while no difference was seen between crizotinib and alectinib (RR 1.12, 95% CI 0.79–1.59). The next-generation ALK inhibitors alectinib, brigatinib and lorlatinib combined resulted in a similar rate of bradycardia when compared to crizotinib (RR 0.77, 95% CI 0.57–1.04). All ALK inhibitors (as an aggregate) caused more dizziness (as a potential symptom of bradycardia) than standard chemotherapy (RR 1.88, 95% CI 1.44–2.44). Conclusion: Crizotinib for the treatment of NSCLC is associated with a higher risk for bradycardia compared to standard chemotherapy. There is no evidence of a difference in bradycardia risk between crizotinib and newer ALK inhibitors.
- Subjects :
- Pulmonary and Respiratory Medicine
Oncology
Bradycardia
Alectinib
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Brigatinib
medicine.drug_class
Crizotinib
Carcinoma, Non-Small-Cell Lung
hemic and lymphatic diseases
Internal medicine
medicine
Humans
Anaplastic lymphoma kinase
Anaplastic Lymphoma Kinase
Adverse effect
Protein Kinase Inhibitors
business.industry
Lorlatinib
ALK inhibitor
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 01695002
- Volume :
- 161
- Database :
- OpenAIRE
- Journal :
- Lung Cancer
- Accession number :
- edsair.doi.dedup.....7ef1a6b19c064902dce8acc2fdbe17d2