A real-world pharmacovigilance study of dacomitinib based on FDA adverse event reporting system (FAERS) database

Dacomitinib, a second-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor that was approved for the treatment of non-small cell lung cancer in 2018, has limited real-world safety data. This study investigates dacomitinib-associated adverse events (AEs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We conducted a retrospective analysis of the FAERS database, extracting dacomitinib-related reports from 2018 Q3 to 2024 Q3. To assess the association between dacomitinib and AEs, we employed multiple disproportionality analyses, including the reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. From the FAERS database, we analyzed 10,869,881 case reports, identifying 594 dacomitinib-related AEs. Among these, 56 significant PTs were retained based on the four algorithms. Common AEs included diarrhoea (ROR 4.40), rash (ROR 6.40), paronychia (ROR 347.91), mouth ulcers (ROR 32.24), dermatitis acneiform (ROR 58.79), palmar-plantar erythrodysaesthesia (ROR 16.08), liver injury (ROR 5.56), and pulmonary fibrosis (ROR 9.75), aligning with the drug label. In addition, some unanticipated major AEs were detected, including cholestasis (ROR 6.12), cholelithiasis (ROR 6.56), an increase in blood pressure (ROR 6.85), an elevation in heart rate (ROR 4.91), a decline in red blood cell count (ROR 5.95), a decrease in hemoglobin (ROR 5.95), the presence of pericardial effusion (ROR 5.59), white matter lesions (ROR 98.11), and cerebral atrophy (ROR 56.69). All reported RORs for the identified AEs were statistically significant, as defined by a lower limit of the 95% confidence interval that exceeded 1. This study systematically evaluates AEs associated with dacomitinib, confirming its known safety profiles and identifying some emerging safety concerns in real-world settings. These findings provide crucial insights for clinicians and pharmacists to better manage dacomitinib's safety profile.