Deep exploration of sotorasib-related hepatobiliary AEs: Based on FDA Adverse Event reporting system

This study focused on the exploration of sotorasib-related hepatobiliary adverse events (AEs) through the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, to provide reference for safe clinical use.

We extracted sotorasib AEs report data from FAERS database from May 28, 2021 to September 30, 2024. Four algorithms were used for disproportionality analysis to comprehensively identify AEs signals related to sotorasib, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi item gamma Poisson shrinker (MGPS). We focused on analyzing and evaluating the signals of hepatobiliary AEs and described their characteristics and risk factors.

We collected 2383 AEs with sotorasib as the main suspected drug. Among them, 291 cases were related to hepatobiliary AEs, involving 36 PTs, of which 15 PTs had positive signals. Eleven PTs in the positive signals were identified not listed in the drug instructions, among which hepatic function abnormal, cholestasis, and cholestatic liver injury had strong signals. There was still a correlation between sotorasib and hepatobiliary AEs after analyzed by gender, age, reporter type, and serious reports, but the atlas was different in the hierarchical scheme. Hepatotoxicity and drug-induced liver injury were classified as moderate clinical priority and should be given priority in clinical practice.

This study obtained the real hepatobiliary toxicity spectrum, characteristics, and influencing factors of sotorasib through FAERS data mining, which provides valuable insights for healthcare professionals to effectively manage the risk of sotorasib-related hepatobiliary AEs in clinical practice.