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Cardiovascular Toxicities of Selective Ret-specific Tyrosine Kinase Inhibitors: a Pharmacovigilance Study Based on the United States Food and Drug Administration Adverse Event Reporting System Database

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Specialty Pharmacology
Date 2024 Aug 13
PMID 39137926
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Abstract

Background: Selective RET-specific tyrosine kinase inhibitors (RET-TKIs) treat RET fusion-positive non-small cell lung cancer (NSCLC), but studies on their cardiovascular toxicities are limited. This study aimed to characterize the cardiovascular toxicities associated with selective RET-TKI in real-world settings.

Research Design And Methods: Data from the United States Food and Drug Administration Adverse Event Reporting System database from 1 January 2020 to 30 June 2023, were analyzed. Two disproportionality methods, information component and reporting odds ratio (ROR) were used.

Results: Both pralsetinib and selpercatinib showed positive signals for hypertension (pralsetinib: ROR: 5.25, 95% CI: 4.40-6.26; selpercatinib: ROR: 2.68, 95% CI: 1.87-3.82). Additionally, pralsetinib showed a positive signal for ischemic heart disease (ROR: 3.92, 95% CI: 2.94-5.23), and selpercatinib for torsade de pointes/QT prolongation (ROR: 2.65, 95% CI: 1.74-4.04). The median time to onset(TTO) of cardiovascular toxicities was 33 days (IQR: 9-73 days) for pralsetinib and 15 days (IQR: 10-50 days) for selpercatinib. The proportion of deaths, life-threatening events, and hospitalizations due to cardiovascular toxicities were 8.57%, 1.19%, and 31.43%, respectively, for total selective RET-TKI.

Conclusions: Selective RET-TKIs are related to multiple cardiovascular toxicities. Pralsetinib was linked to ischemic heart disease, and selpercatinib to torsade de pointes/QT prolongation and thrombotic events.

Citing Articles

Matters of the Heart: Cardiotoxicity Related to Target Therapy in Oncogene-Addicted Non-Small Cell Lung Cancer.

Torresan S, Bortolot M, De Carlo E, Bertoli E, Stanzione B, Del Conte A Int J Mol Sci. 2025; 26(2).

PMID: 39859270 PMC: 11765312. DOI: 10.3390/ijms26020554.