Disproportionality of Adverse Events to KRAS G12C Inhibitors Based on the FAERS Database

doi:10.19803/j.1672-8629.20240841

Abstract

Abstract: Objective To analyze the adverse event signals of KRAS G12C inhibitors, sotorasib and adagrasib, so as to provide a reference for clinical safety. Methods Data on adverse events reported from Q3 2021 to Q2 2024 was retrieved from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database before related signals were mined using the reporting odds ratio (ROR), the comprehensive standard method of the Medicines and Healthcare Products Regulatory Agency (MHRA), the Information Component (IC) method, and the Empirical Bayes Geometric Mean (EBGM) method. Results Sotorasib was primarily associated with adverse reactions related to hepatobiliary disorders (n=329, IC₀₂₅=3.06), with the strongest signal for hepatotoxicity (n=76, IC₀₂₅=5.14) while adagrasib was associated with surgical and medical procedures (n=102, IC₀₂₅=1.65) and metabolism and nutrition disorders (n=76, IC₀₂₅=0.97), with the strongest signal for electrocardiogram QT prolonged (n=11, IC₀₂₅=2.87). Rare reactions included pulmonary embolism for sotorasib and status epilepticus for adagrasib. Gender and cumulative doses made a big difference to the incidence of adverse reactions. Conclusion In clinical application, it is necessary to strengthen the monitoring of adverse reactions of sotorasib and adaglasib, especially rare and serious adverse reactions, to improve drug safety.

Key words: KRAS G12C Inhibitors, Sotorasib, Adagrasib, Adverse Drug Event, Liver Toxicity, QT Interval Prolongation on Electrocardiogram, Neurotoxicity, FAERS

CLC Number:

ZHU Zhipeng, LYU Qiang, YE Xiaofei, GUO Xiaojing. Disproportionality of Adverse Events to KRAS G12C Inhibitors Based on the FAERS Database[J]. Chinese Journal of Pharmacovigilance, 2025, 22(3): 297-304.

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