Safety signals of zolbetuximab in gastric or gastroesophageal junction adenocarcinoma: a comprehensive analysis of the FDA adverse event reporting system (FAERS) data.

BACKGROUND

Zolbetuximab is a novel monoclonal antibody targeting CLDN18.2 for advanced gastric or gastroesophageal junction adenocarcinoma. However, its large-scale, real-world safety profile remains incompletely characterized. This study aimed to analyze its post-marketing adverse events using the FDA Adverse Event Reporting System (FAERS).

METHODS

Adverse event reports from FAERS (Q1 2024 - Q3 2025) with zolbetuximab as the primary suspect were analyzed. Disproportionality analysis using four algorithms (ROR, PRR, IC, and EBGM) was performed to detect potential safety signals. Time-to-onset analysis was also conducted.

RESULTS

A total of 676 reports were analyzed. Disproportionality analysis confirmed known gastrointestinal and metabolic disorders while identifying several unlabeled adverse events, including but not limited to gastritis, protein-losing gastroenteropathy, peripheral edema, compression fracture, and vascular pain. The median time-to-onset was 0 days, with 82.9% of events occurring within the first 30 days.

CONCLUSION

This first large-scale pharmacovigilance study of zolbetuximab detected several potential safety signals not currently listed in the prescribing information. These findings highlight the importance of post-marketing surveillance and should be interpreted as hypothesis-generating, warranting further validation in clinical and real-world studies.