Zolbetuximab-associated adverse event reporting signals in gastric cancer: a FAERS disproportionality analysis

Zolbetuximab has an established upper gastrointestinal tolerability profile, but the broader post-marketing spectrum of gastric mucosal events and findings related to albumin, protein loss, and fluid balance remains incompletely characterized.

We conducted an indication-restricted, report-level US Food and Drug Administration Adverse Event Reporting System (FAERS) analysis from 2024 Q1 through 2026 Q1, comparing 597 zolbetuximab reports with 1,231 pooled nivolumab/pembrolizumab reports. Reporting odds ratios (RORs) were used for primary screening, with five contextual reporting backgrounds, adjusted Firth models, and chemotherapy-, drug-role-, geographic-, calendar-time-, and submission-channel analyses. Time to onset and co-reporting were summarized descriptively.

Among 1,041 screened preferred terms, 58 met the ROR criterion and 48 were clinically retained. The findings clustered into three groups: upper gastrointestinal and intake-related findings, gastric mucosal findings, and findings related to albumin, protein loss, and fluid balance. The eight post hoc focus preferred terms (PTs) retained support across all five backgrounds and the principal adjusted analyses. Gastritis was reported in 22 zolbetuximab versus 1 pooled PD-1 report (ROR 32.07, 95% CI 6.12-167.97), hypoalbuminemia in 72 versus 3 (ROR 48.43, 95% CI: 16.49-142.24), and protein-losing gastroenteropathy (PLE) in 10 versus 2 (ROR 8.79, 95% CI: 2.21-35.04). Japan accounted for 83.8% of zolbetuximab reports, with limited support outside Japan.

The analysis reinforced established upper gastrointestinal findings. Gastritis and findings related to albumin, protein loss, and fluid balance require clinical confirmation, while protein-losing gastroenteropathy was reported sparsely. Overall, the results characterize reporting disproportionality in an early, Japan-dominant setting, not incidence or comparative clinical risk.