A comprehensive exploration of adverse reactions to lapatinib: a disproportionate analysis based on the FAERS database

Lapatinib, an FDA-approved tyrosine kinase inhibitor, treats HER2+ advanced/metastatic breast cancer. This study comprehensively analyzed its adverse reaction profile using FDA Adverse Event Reporting System (FAERS) to guide clinical use. Adverse event (AE) reports for lapatinib from the second quarter of 2007 to the second quarter of 2024 in FAERS were analyzed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinkage (MGPS) and Bayesian Confidence Propagation Neural Network (BCPNN) to identify AE signals. Among 8300 AE reports, females (91.47%) and ages 40–59.9 (33.71%) were predominant. 20 system organ classifications (SOCs) were affected, with gastrointestinal disorders (ROR = 3.46) and skin disorders (ROR = 2.47) most significant. Based on the PT level, a total of 111 PTs were analyzed that met the four algorithms, including typical AEs such as diarrhea (<i>n</i> = 3410), vomiting (<i>n</i> = 856), and rash (<i>n</i> = 856), as well as some rare AEs that were not prompted by the drug inserts, such as neutropenia (<i>n</i> = 252), pericardial effusion (<i>n</i> = 43), lymphedema (<i>n</i> = 20). The majority of lapatinib-associated AEs had onset within 30 days (51%). Lapatinib has a generally favorable safety profile, but gastrointestinal toxicity and dermatotoxicity require close monitoring to prevent serious AEs.

拉帕替尼（Lapatinib）是FDA批准的酪氨酸激酶抑制剂（tyrosine kinase inhibitor），用于治疗HER2阳性晚期/转移性乳腺癌。本研究利用FDA不良事件报告系统（FAERS）全面分析其不良反应特征，以指导临床应用。研究对FAERS中2007年第二季度至2024年第二季度期间拉帕替尼的不良事件（AE）报告进行分析，采用报告比值比（ROR）、比例报告比（PRR）、多项目伽马泊松收缩法（MGPS）及贝叶斯置信传播神经网络（BCPNN）识别AE信号。在8300份AE报告中，女性（91.47%）和40-59.9岁年龄段（33.71%）占主导。20个系统器官分类（SOCs）受影响，其中胃肠道疾病（ROR=3.46）和皮肤疾病（ROR=2.47）最为显著。基于PT水平，共分析符合四种算法的111个PT，包括腹泻（n=3410）、呕吐（n=856）、皮疹（n=856）等典型AE，以及药物说明书未提及的罕见AE如中性粒细胞减少症（neutropenia）、心包积液（pericardial effusion）、淋巴水肿（lymphedema）。多数拉帕替尼相关AE在30天内发生（51%）。拉帕替尼总体安全性良好，但胃肠道毒性（gastrointestinal toxicity）和皮肤毒性（dermatotoxicity）需密切监测以预防严重AE。