Zhang Huiping, Di Man, Wang Jingjing, Wang Shan, Dai Yini, Huang Jingjing, Zhou Zhuo
Department of Obstetrics and Gynecology, Northwest University First Hospital, Xi'an, Shaanxi, China.
Department of Obstetrics and Gynecology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China.
Front Pharmacol. 2025 Aug 15;16:1622339. doi: 10.3389/fphar.2025.1622339. eCollection 2025.
Pembrolizumab is a key drug in the immunotherapy of endometrial cancer (EC) and has improved the prognosis to some extent. However, adverse drug events (ADEs) have hindered the achievement of expected therapeutic outcomes in EC. This study, therefore, aims to investigate the ADEs of pembrolizumab using the FAERS database, offering new insights for clinical practice in EC treatment.
From the first quarter of 2016 to the first quarter of 2025, ADEs associated with pembrolizumab in EC were collected from the FAERS database. The Reporting Odds Ratio (ROR) was used as the primary analytical method for signal detection. To validate the robustness of the results, three additional algorithms-Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS)-were also applied. ADEs were systematically classified using the Medical Dictionary for Regulatory Activities (MedDRA) into System Organ Classes (SOC) and Preferred Terms (PT), and ranked by both frequency and signal strength.
A total of 2,154 ADEs associated with pembrolizumab in the treatment of EC were retrieved from the FAERS database. The age distribution of ADEs was primarily concentrated in the 65-85 years age group. The reported body weights were mainly in the 50-100 kg range. The most frequent ADE outcome was hospitalization. The majority of ADEs occurred within 0-30 days after pembrolizumab administration. Identified ADEs involved endocrine system disorders, including Increased Thyroid Hormones (ROR = 9.22), Decreased Thyroid Hormones (ROR = 5.31), and Immune-Mediated Hypothyroidism (ROR = 6.16). Skin and subcutaneous tissue disorders included Pruritic Rash (ROR = 3.16) and Blisters (ROR = 3.06). Liver-related issues included Increased Hepatic Enzymes (ROR = 2.25). These key signals were consistently confirmed by additional disproportionality algorithms, including PRR, BCPNN, and MGPS, reinforcing the robustness of the findings.
This study used the FAERS database to identify frequently reported ADEs associated with pembrolizumab in the treatment of EC, including endocrine system diseases, musculoskeletal system disorders, skin and subcutaneous tissue reactions, and hepatotoxicity. These findings provide crucial evidence for risk stratification and safety monitoring in clinical practice, emphasizing the need for vigilance toward specific organ systems during the 0-30-day treatment window.
帕博利珠单抗是子宫内膜癌（EC）免疫治疗中的关键药物，在一定程度上改善了预后。然而，药物不良事件（ADEs）阻碍了EC预期治疗效果的实现。因此，本研究旨在利用美国食品药品监督管理局不良事件报告系统（FAERS）数据库调查帕博利珠单抗的ADEs，为EC治疗的临床实践提供新的见解。
收集2016年第一季度至2025年第一季度FAERS数据库中与EC患者使用帕博利珠单抗相关的ADEs。报告比值比（ROR）用作信号检测的主要分析方法。为验证结果的稳健性，还应用了另外三种算法——比例报告比值比（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项目伽马泊松收缩器（MGPS）。使用《医学监管活动医学词典》（MedDRA）将ADEs系统分类为系统器官类别（SOC）和首选术语（PT），并按频率和信号强度进行排名。
从FAERS数据库中检索到总共2154例与帕博利珠单抗治疗EC相关的ADEs。ADEs的年龄分布主要集中在65 - 85岁年龄组。报告的体重主要在50 - 100千克范围内。最常见的ADE结果是住院。大多数ADEs发生在帕博利珠单抗给药后的0 - 30天内。确定的ADEs涉及内分泌系统疾病，包括甲状腺激素升高（ROR = 9.22）、甲状腺激素降低（ROR = 5.31）和免疫介导的甲状腺功能减退（ROR = 6.16）。皮肤和皮下组织疾病包括瘙痒性皮疹（ROR = 3.16）和水泡（ROR = 3.06）。肝脏相关问题包括肝酶升高（ROR = 2.25）。这些关键信号通过PRR、BCPNN和MGPS等额外的不成比例算法得到了一致确认，加强了研究结果的稳健性。
本研究利用FAERS数据库识别了EC治疗中与帕博利珠单抗相关的常见报告ADEs，包括内分泌系统疾病、肌肉骨骼系统疾病、皮肤和皮下组织反应以及肝毒性。这些发现为临床实践中的风险分层和安全监测提供了关键证据，并强调在0 - 30天治疗窗口期间对特定器官系统保持警惕的必要性。
