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Updated: May 10, 2025

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Two first-generation KRAS inhibitor safety profiles: a disproportionality analysis of individual reports from the FDA

Ying Zhang1, Shuhua Tong1, Li Wan1

  • 1Department of Pharmacy, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, China.

Expert Opinion on Drug Safety
|April 28, 2025
PubMed
Abstract

Insights

First-generation KRAS inhibitors, sotorasib and adagrasib, show specific adverse events like diarrhea and hepatotoxicity. This analysis highlights the need for careful patient monitoring during cancer treatment.

Area of Science:

  • Oncology
  • Pharmacovigilance
  • Drug Safety

Background:

  • Sotorasib and adagrasib are approved first-generation KRAS inhibitors for specific cancers.
  • This study evaluates adverse events (AEs) associated with these KRAS inhibitors using FAERS data.

Purpose of the Study:

  • To assess the safety profile of sotorasib and adagrasib.
  • To identify potential new adverse event signals for KRAS inhibitors.

Main Methods:

  • Utilized the FAERS database for adverse event reporting.
  • Applied four disproportionality analysis methods: ROR, PRR, BCPNN, and MGPS.
  • Analyzed 5,580 AEs from 2,958 reports between Q2 2021 and Q1 2024.

Main Results:

  • Identified 43 and 18 disproportionate reporting items for sotorasib and adagrasib, respectively.
  • Common AEs included diarrhea, hepatotoxicity, and pneumonitis.
  • Unexpected AEs such as pericardial effusion (sotorasib) and seizure (adagrasib) were noted, with most occurring within the first month of treatment.

Conclusions:

  • The study provides a comprehensive safety profile for KRAS inhibitors.
  • Highlights the emergence of new AE signals, underscoring the need for vigilant monitoring and supportive care in patients receiving these treatments.
Keywords:
FAERSKRAS inhibitorSotorasibadagrasibpharmacovigilance

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