Cardiovascular toxicities of selective ret-specific tyrosine kinase inhibitors: a pharmacovigilance study based on

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Yinjing Hou1, Xiayang Ren2, Ying Chen1

  • 1Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Expert Opinion on Drug Safety
|August 13, 2024
PubMed
Abstract

Insights

Selective RET tyrosine kinase inhibitors (RET-TKIs) used for non-small cell lung cancer can cause cardiovascular issues like hypertension and heart disease. Real-world data reveal specific risks for pralsetinib and selpercatinib, including ischemic heart disease and QT prolongation.

Area of Science:

  • Oncology
  • Cardiology
  • Pharmacovigilance

Background:

  • Selective RET tyrosine kinase inhibitors (RET-TKIs) are crucial for treating RET fusion-positive non-small cell lung cancer (NSCLC).
  • Limited real-world data exist on the cardiovascular toxicities associated with these targeted therapies.
  • This study addresses the need to characterize cardiovascular risks of RET-TKIs in clinical practice.

Purpose of the Study:

  • To investigate and characterize the cardiovascular toxicities of selective RET-TKIs in a real-world setting.
  • To identify specific cardiovascular adverse events linked to pralsetinib and selpercatinib.
  • To assess the incidence and nature of cardiovascular events associated with RET-TKI treatment.

Main Methods:

  • Analysis of the US Food and Drug Administration Adverse Event Reporting System database (January 2020 - June 2023).
  • Utilized disproportionality analyses, including information component and reporting odds ratio (ROR).
  • Evaluated cardiovascular adverse events, time to onset, and outcomes such as death, life-threatening events, and hospitalizations.

Main Results:

  • Both pralsetinib and selpercatinib showed significant positive signals for hypertension.
  • Pralsetinib was associated with ischemic heart disease (ROR: 3.92), while selpercatinib was linked to torsade de pointes/QT prolongation (ROR: 2.65).
  • Median time to cardiovascular toxicity onset was 33 days for pralsetinib and 15 days for selpercatinib; overall cardiovascular events led to death in 8.57% of cases.

Conclusions:

  • Selective RET-TKIs are associated with a spectrum of cardiovascular toxicities.
  • Pralsetinib use is linked to ischemic heart disease, and selpercatinib to torsade de pointes/QT prolongation and thrombotic events.
  • These findings highlight the importance of cardiovascular monitoring during RET-TKI therapy for NSCLC patients.
Keywords:
Cardiovascular toxicitiesFood and Drug Administration Adverse Event Reporting SystemSelective ret-specific tyrosine kinase inhibitorsdisproportionality analysisnon-small cell lung cancer

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