Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Associated Cardiotoxicity: A Recent Five-Year Pharmacovigilance
Yihan Liu1,2,3,4, Chen Chen4,5, Chencheng Rong4
1Department of Pharmacy, West China Second Hospital, Sichuan University, Chengdu, China.
Abstract:
Background: Clinical trials frequently reported anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) associated with cardiac adverse drug events (AEs) but minimal postmarketing data. We aimed to research real-world cardiac disorders associated with ALK-TKIs based on the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Extract reports from the FAERS from the first quarter of 2016 to the second quarter of 2021 were obtained. Data mining of cardiac disorders associated with ALK-TKIs was carried out using disproportionality analysis to determine the clinical characteristics of AEs. Results: In total, 605 cases were screened out. These events were found to be more prevalent in patients ≥45 years (50.74%) and women (50.74%). The onset time of cardiac disorders was variable and concentrated within 2 months, with a median time of 33 days. The outcomes tended to be poor, with 20.93% fatality proportion. Cardiac arrhythmia was a common adverse event of ALK-TKIs, especially bradycardia. Crizotinib and lorlatinib showed positive signals in cardiac disorders, especially in heart failure, and brigatinib presented no signals. The study also found that myocarditis caused by ceritinib and cardiomyopathy caused by lorlatinib may be potential new adverse drug reactions. Conclusion: ALK-TKIs were reported more frequently in cardiotoxicity than other drugs and could often manifest earlier. We also found potential new AE signals in specific drugs and need more clinical studies to confirm. Our study helps fill the safety information of ALK-TKIs in the heart and provides directions for further research.
Insights
Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) can cause cardiac adverse events, including arrhythmia and heart failure, particularly in older women. Further research is needed to confirm potential new reactions like myocarditis and cardiomyopathy.
Area of Science:
- Oncology
- Pharmacovigilance
- Cardiology
Background:
- Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) are used in cancer treatment.
- Clinical trials suggest ALK-TKIs are linked to cardiac adverse drug events (AEs).
- Limited postmarketing data exists on ALK-TKI-associated cardiac AEs.
Purpose of the Study:
- To investigate real-world cardiac disorders associated with ALK-TKIs.
- To analyze cardiac AEs using the Food and Drug Administration Adverse Event Reporting System (FAERS).
Main Methods:
- Extracted FAERS data from Q1 2016 to Q2 2021.
- Employed disproportionality analysis to identify cardiac AEs linked to ALK-TKIs.
- Examined clinical characteristics and onset times of reported cardiac events.
Main Results:
- Identified 605 cases of cardiac disorders associated with ALK-TKIs.
- Events were more common in patients aged 45 and older (50.74%) and women (50.74%).
- Cardiac arrhythmia, particularly bradycardia, was frequent; crizotinib and lorlatinib showed signals for heart failure; brigatinib showed none. Myocarditis (ceritinib) and cardiomyopathy (lorlatinib) may be new AEs.
Conclusions:
- ALK-TKIs are frequently associated with cardiotoxicity, often manifesting early.
- Specific ALK-TKIs like crizotinib and lorlatinib show cardiac risks, while brigatinib appears safer.
- Potential new AEs, including myocarditis and cardiomyopathy, require further clinical investigation to confirm safety profiles.
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