Adverse drug reaction assessment of pembrolizumab and nivolumab in esophageal cancer treatment based on the US FAERS database

Background: Esophageal cancer (EC) is one of the most aggressive malignant tumors, associated with high mortality rates. Pembrolizumab and nivolumab have been incorporated into immunotherapy regimens for advanced EC, but immune-related adverse events (irAEs) remain a major factor affecting antitumor efficacy. This study aims to conduct a comprehensive and systematic analysis of adverse events (AEs) associated with pembrolizumab and nivolumab in EC immunotherapy using the FAERS database, providing new insights to optimize clinical practice. Methods: All AE reports related to pembrolizumab in EC were extracted from the FAERS database. Disproportionality analyses were performed using three algorithms, including the ROR, PRR, BCPNN. Based on Kaplan-Meier analysis with log-rank tests, the median time to onset and associated risk factors for relevant AEs were determined. Finally, univariable logistic regression analysis was used to identify risk factors for death associated with AEs. Result: A total of 3,669 AE reports related to pembrolizumab and 4,308 AE reports related to nivolumab were identified. Descriptive analysis showed that the number of AE reports increased year by year, and the number of reports was higher in the elderly population. The United States, Japan, and China were the primary reporting countries. The overall median time to onset for pembrolizumab-related PTs was 35 days, while that for nivolumab-related PTs was 52 days. In pembrolizumab, age ≥ 65 years was a risk factor for shorter median onset time, whereas in nivolumab, female gender was a risk factor for shorter median onset time. Among pembrolizumab-related AEs, weight was associated with a higher mortality risk. For nivolumab-related AEs, age, weight, increased cumulative number of adverse reactions, and earlier median onset time were associated with higher mortality risk. Conclusion: This real-world study is the first to analyze pembrolizumab and nivolumab irAEs in EC using the FAERS database, identifying high-signal events such as endocrine, hepatic, renal, gastrointestinal toxicities. Additional cardiovascular and pulmonary events are observed. Female and older patients experienced earlier irAEs. Increased mortality risk was associated with weight, cumulative number of AEs, and earlier irAE onset. These findings can guide personalized treatment, early intervention, and improve prognosis.