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Post-marketing safety concerns of sotorasib: A disproportionality analysis based on FDA adverse event reporting
Yiling Ding1, Hongyan Su2, Yamin Shu1
1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Background:
Sotorasib has been approved for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Due to the limitations of clinical trials, potential adverse events (AEs) and long-term safety issues cannot be detected. The presented study aimed to evaluate sotorasib-associated AEs using the FDA Adverse Event Reporting System (FAERS) database.
Methods:
Post-marketing AE reports of sotorasib in the database were collected for analysis. Disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) and empirical bayes geometric mean (EBGM) algorithms, were performed to mine the signals of sotorasib-associated AEs. The median duration, quartiles and the Weibull shape parameter (WSP) test were used to assess the onset time data.
Results:
The database contained 1538 cases of sotorasib as primary suspect (PS), with 27 signals detected, scattering in 5 SOCs. The SOC of hepatobiliary disorders (182, ROR 4.48, PRR 4.07, IC 2.02, EBGM 4.07) met the four methodological thresholds. The median onset time of sotorasib-associated AEs was 42 days (interquartile range [IQR] 14-86.75 days). Different SOCs had different types of risk over time.
Conclusion:
After obtaining marketing authorization, the study identified all potentially relevant adverse event (AE) signals expected to have a reporting frequency higher than anticipated and characterized them during sotorasib treatment.
Insights
This study analyzed FDA Adverse Event Reporting System data to identify safety signals for sotorasib, a KRAS G12C inhibitor for non-small cell lung cancer. Hepatobiliary disorders emerged as a key safety concern requiring monitoring.
Area of Science:
- Oncology
- Pharmacovigilance
- Drug Safety
Background:
- Sotorasib is approved for KRAS G12C-mutated non-small cell lung cancer (NSCLC).
- Clinical trials have limitations in detecting rare or long-term adverse events (AEs).
- Post-marketing surveillance is crucial for comprehensive drug safety assessment.
Purpose of the Study:
- To evaluate sotorasib-associated AEs using the FDA Adverse Event Reporting System (FAERS) database.
- To identify and characterize potential safety signals for sotorasib.
- To assess the onset time of sotorasib-related adverse events.
Main Methods:
- Utilized FAERS database for post-marketing AE reports of sotorasib.
- Performed disproportionality analyses (ROR, PRR, IC, EBGM) to detect AE signals.
- Assessed AE onset time using median duration, quartiles, and Weibull shape parameter (WSP) test.
Main Results:
- Identified 27 AE signals across 5 Systems of Organ Classification (SOCs) from 1538 sotorasib primary suspect cases.
- Hepatobiliary disorders emerged as a significant safety signal (ROR 4.48, PRR 4.07, IC 2.02, EBGM 4.07).
- Median onset time for sotorasib-associated AEs was 42 days, with varying risk profiles over time across different SOCs.
Conclusions:
- The study successfully identified potential adverse event signals for sotorasib post-marketing.
- Hepatobiliary disorders represent a key area for monitoring sotorasib safety.
- Characterizing AE signals and onset times aids in managing sotorasib treatment risks.
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