Real-world pharmacovigilance of adverse events associated with immune checkpoint and targeted inhibitors in digestive system tumors: A FAERS database study.

ObjectiveDigestive system tumors (DST) remain a major contributor to the global cancer burden. This study aimed to characterize the adverse events (AEs) spectrum, identify potential safety signals, and explore subgroup-specific reporting patterns and time-to-onset features of immune checkpoint and targeted inhibitors in DST using the FDA Adverse Event Reporting System (FAERS).MethodsThis was a retrospective observational pharmacovigilance study based on spontaneous reports submitted to FAERS from 2004Q1 to 2024Q4. The study population comprised FAERS reports involving patients with DST who received PD-1, PD-L1, CTLA-4, HER2, EGFR, VEGF, or VEGFR inhibitors. Reports were retrieved through OpenVigil 2.1 and coded using Medical Dictionary for Regulatory Activities preferred terms. After data cleaning, disproportionality analyses were performed using the reporting odds ratio and information component, with signal thresholds defined as ROR025 >1, IC025 >0, and at least three reports. Descriptive analyses, temporal trend analyses, subgroup analyses, and Weibull time-to-onset analyses were also conducted.ResultsA total of 41,168 eligible reports were included. Most reports involved male patients and individuals weighing 50-100 kg. VEGFR inhibitors accounted for the largest number of AE reports, whereas CTLA-4 inhibitors accounted for the fewest. Reporting trends generally increased over time, although fluctuations were observed across drug classes. At the preferred-term level, 131, 372, 38, 114, 274, 382, and 320 valid safety signals were identified for PD-1, PD-L1, CTLA-4, HER2, EGFR, VEGF, and VEGFR inhibitors, respectively. Frequently detected signals included disease progression, off-label use, and death. Stratified analyses suggested age- and sex-related differences in the reporting patterns of selected AEs across drug classes. Time-to-onset analysis showed an early-failure pattern for all investigated inhibitors, with the hazard of AE occurrence decreasing over time.ConclusionsThis FAERS-based retrospective pharmacovigilance study comprehensively characterized the AE reporting profiles of immune checkpoint and targeted inhibitors in DST. Multiple potential safety signals, subgroup-specific reporting patterns, and early-onset AE features were identified. These findings may support clinical risk monitoring, pharmacovigilance surveillance, and individualized safety assessment in patients with DST receiving immune checkpoint or targeted inhibitors.