Huang Shuohan, Guo Zihan, Wang Mengmeng, She Youjun, Ye Xuan, Zhai Qing, Liu Jiyong, Du Qiong
Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Expert Opin Drug Saf. 2023 Feb;22(2):175-181. doi: 10.1080/14740338.2023.2189235. Epub 2023 Mar 10.
BRAF and MEK inhibitor combination therapy have significantly improved the outcome of several BRAF-mutation tumors, but it also confers the risk of drug-induced ocular adverse events (oAEs). However, very few studies focused on this risk.
The United States Food and Drug Administration Adverse Event Reporting System (FAERS) data from Quarter 1-2011 to Quarter 2-2022 were searched to detect signs of oAEs of three marketed BRAF and MEK inhibitor combination therapies: vemurafenib plus cobimetinib (V + C), dabrafenib plus trametinib (D + T), and encorafenib plus binimetinib (E + B). Disproportionality analyses were performed by calculating the proportional reporting ratio (PRR), χ2 (chi-square), and reporting odds ratios (RORs) with a 95% confidence interval (CI).
A series of oAEs were identified, including 42 preferred terms, which could be classified into 8 aspects. In addition to previously reported oAEs, several unexpected oAE signals were detected. Moreover, differences in oAE profiles were found among three combination therapies (V + C, D + T, and E + B).
Our findings support an association between several oAEs and BRAF and MEK inhibitor combination therapies, including several new oAEs. In addition, oAEs profiles may vary across the treatment regimens. Further studies are needed to better quantify these oAEs.
BRAF和MEK抑制剂联合疗法显著改善了几种BRAF突变肿瘤的治疗结果，但也带来了药物性眼部不良事件（oAE）的风险。然而，很少有研究关注这一风险。
检索美国食品药品监督管理局不良事件报告系统（FAERS）2011年第一季度至2022年第二季度的数据，以检测三种已上市的BRAF和MEK抑制剂联合疗法（维莫非尼加考比替尼（V + C）、达拉非尼加曲美替尼（D + T）和恩考芬尼加比美替尼（E + B））的oAE迹象。通过计算比例报告率（PRR）、χ2（卡方）和报告比值比（ROR）及95%置信区间（CI）进行不成比例分析。
识别出一系列oAE，包括42个首选术语，可分为8个方面。除了先前报告的oAE外，还检测到一些意外的oAE信号。此外，在三种联合疗法（V + C、D + T和E + B）之间发现了oAE特征的差异。
我们的研究结果支持几种oAE与BRAF和MEK抑制剂联合疗法之间存在关联，包括几种新的oAE。此外，不同治疗方案的oAE特征可能有所不同。需要进一步研究以更好地量化这些oAE。
