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

Yinjing Hou; Xiayang Ren; Ying Chen; Yanfeng Wang

doi:10.1080/14740338.2024.2392003

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

Expert Opin Drug Saf. 2024 Aug 19:1-9. doi: 10.1080/14740338.2024.2392003. Online ahead of print.

Authors

Yinjing Hou¹, Xiayang Ren², Ying Chen¹, Yanfeng Wang³

Affiliations

¹ Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
² Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

PMID: 39137926
DOI: 10.1080/14740338.2024.2392003

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.

Keywords: Cardiovascular toxicities; Food and Drug Administration Adverse Event Reporting System; Selective ret-specific tyrosine kinase inhibitors; disproportionality analysis; non-small cell lung cancer.