Signal mining study of third-generation EGFR-TKI olmutinib based on adverse reaction signals from FAERS database

WANG Zi-hao; YAN Sen

doi:10.20251/j.cnki.1003-3734.2025.08.015

Abstract：Objective:To mine and analyze adverse reaction signals of olmutinib,an epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor(TKl),for safe and rational clinical use.Methods:Adverse event reports of olmutinib from October 2012 to June 2023 were collected from the FAERS database,the adverse event reporting system of the U.S.FDA.The adverse drug event(ADE)reports were statistically described from the perspectives of year-to-year presentation trends,gender and age of patients,and serious adverse events as described above.The data were mined and analyzed using reporting odds ratio(ROR),proportionate reporting ratio(PRR),and Bayesian confidence progressive neural network(BCPNN)methods of the proportional imbalance method to detect the safety signals of olmutinib and analyze the key involved organs and high-risk signals.Results:A total of 63 726 reports of adverse reactions were collected with olmutinib as the first suspected(PS)drug,among which female patients had higher percentage(66.0％)than male patients(27.7％).The reports mainly concentrated in the age groups of 18～44 years(23.8％),60～74 years(19.2％),and ≥75 years(19.2％),and included cases susceptible to death(40.09％),hospitalization(20.80％),and other serious adverse effects.Three data mining methods were applied to detect 386 co-positive signals,and the top five cumulative organs of olmutinib were gastrointestinal diseases(11.1％),respiratory and thoracic mediastinum diseases(10.1％),abnormalities in the indicators of various examinations and medical tests(9.3％),all kinds of neurological diseases(7.0％),and diseases of the skin and subcutaneous tissues(6.2％),and the top five ADRs in signal intensity were gastrointestinal edema(BCPNN 95％CI=7.07),acute promyelocytic leukemia(BCPNN 95％CI=7.05),uveitis(BCPNN 95％CI=6.78),sinus disease(BCPNN 95％CI=6.43),and EGFR gene mutation(BCPNN 95％CI=6.36).Conclusion:Olmutinib can cause symptoms of gastrointestinal system and respiratory system,as well as various types of neurological disorders,which should be closely monitored by clinical medical workers during treatment.Attention should also be paid to the stronger signals of olmutinib,new ADRs(gastrointestinal edema,acute promyelocytic leukemia),serious ADEs(death,hospitalization,etc.),and to female patients and key age groups.