Pharmacovigilance study of adverse reactions of anti-HER-2 drugs for the treatment of HER-2-positive breast cancer based on the FAERS database.

Objective: There are three categories of drugs that treat human epidermal growth factor receptor type 2 (HER-2) positive breast cancer: monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). The purpose of this study is to analyze and compare the adverse reactions of three classes of anti-HER-2 drugs to various body systems in patients based on the FDA Adverse Event Reporting System (FAERS).

Methods: All data reports were extracted from the FAERS between 2004 and 2024. Data mining of adverse events associated with anti-HER-2 drugs was carried out using disproportionality analysis. A multivariate logistic regression analysis was conducted to explore the risk factors associated with AEs leading to hospitalization.

Results: A total of 47,799 patients were screened for the three classes of drugs, among which ADC drugs caused the largest proportion of deaths. MAb has the strongest ADR signals associated with "cardiac disorders". Moreover, trastuzumab was associated with a greater risk of cardiotoxicity. Logistic regression analysis revealed that the treatment with mAbs should be wary of serious adverse reactions in "infections and infestations" and "metabolism and nutrition disorders". Moreover, "endocrine disorders" were the factor associated with the highest risk of prolonged hospitalization due to trastuzumab deruxtecan (T-DXd). The safety of tucatinib among TKI drugs is greater than that of other drugs.

Conclusion: In general, from the perspective of the effects of the three classes of drugs on the various body systems of patients, we should focus on mAb-associated "cardiac disorders", ADC-associated "hepatobiliary disorders", "respiratory, thoracic and mediastinal disorders", and TKI-associated "gastrointestinal disorders.