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Hepatobiliary Adverse Events Associated With the KRAS p.G12C Inhibitor Sotorasib
1Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Purpose:
The p.G12C mutation in KRAS is commonly found in many cancers and was previously untreatable until drugs like sotorasib were developed. However, up to 15% of patients treated with sotorasib have experienced hepatobiliary adverse events. To investigate whether these side effects are more common among sotorasib users, a pharmacovigilance study is necessary.
Methods:
This study used the FDA adverse event reporting system (FAERS) database, a publicly available repository of reported drug adverse events, and AERSMine, an open-access pharmacovigilance tool, to investigate these adverse events.
Results:
A total of 428 hepatobiliary adverse events were linked to sotorasib. Hepatic cytolysis had the highest reported relative risk at 26.541 and a safety signal of 4.726. Elevated liver and biliary enzymes such as AST, ALT, ALP, and GGT were commonly observed, but with lower reported relative risk and safety signal values, which supports previous real-world reports.
Conclusions:
These findings highlight the hepatobiliary risks associated with sotorasib and underscore the importance of closely monitoring liver function in patients who are using the medication. This is particularly crucial for patients with hepatobiliary cancers, as disease progression and adverse events could be misinterpreted.
Insights
Sotorasib, a KRAS p.G12C inhibitor, is linked to significant hepatobiliary risks. This pharmacovigilance study identified 428 adverse events, with hepatic cytolysis showing a high relative risk, necessitating careful liver function monitoring in patients.
Area of Science:
- Oncology
- Pharmacology
- Hepatology
Background:
- The KRAS p.G12C mutation is prevalent in various cancers.
- Sotorasib is a targeted therapy for KRAS p.G12C-mutated cancers.
- Hepatobiliary adverse events are a known concern with sotorasib treatment.
Purpose of the Study:
- To investigate the incidence and characteristics of hepatobiliary adverse events associated with sotorasib.
- To assess the safety profile of sotorasib concerning liver and biliary function.
- To determine if hepatobiliary adverse events are significantly more common in sotorasib users.
Main Methods:
- Utilized the FDA Adverse Event Reporting System (FAERS) database.
- Employed AERSMine, an open-access pharmacovigilance tool, for data analysis.
- Analyzed reported adverse events linked to sotorasib, focusing on hepatobiliary outcomes.
Main Results:
- Identified 428 hepatobiliary adverse events associated with sotorasib.
- Hepatic cytolysis exhibited the highest relative risk (26.541) and safety signal (4.726).
- Commonly observed elevations in liver enzymes (AST, ALT, ALP, GGT) had lower risk and safety signal values.
Conclusions:
- Sotorasib treatment carries significant hepatobiliary risks.
- Close monitoring of liver function is crucial for patients receiving sotorasib.
- Distinguishing drug-induced events from disease progression is vital, especially in hepatobiliary cancer patients.
