Farooq Asim V, Kaur Savreet, Hundal Pradeep, Burke Maureen, Sulaiman Rosilin, Zahlten-Kümeli Anita, Raoof Sumera, Li Zhezhen, Murias Dos Santos Telma, Huang Xiaojun Jacqueline, Colby Kathryn
University of Chicago Medical Center, Chicago, IL, USA.
Amgen Inc., Thousand Oaks, CA, USA.
Ophthalmol Ther. 2025 May 12. doi: 10.1007/s40123-025-01139-6.
Targeted cancer therapies have transformed the landscape of cancer treatments but are often associated with off-target adverse drug reactions due to overlapping molecular pathways in healthy tissues, including those in the eye. Fibroblast growth factor receptors (FGFRs), expressed across various parts of the eye, can become unintended targets of FGFR inhibitors such as erdafitinib, infigratinib, and pemigatinib, leading to ocular adverse events (AEs) affecting the ocular surface and retina. AEs across clinical trials are graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), which may not completely capture the ocular sequelae resulting from the use of emerging therapies. As CTCAE grading is mainly through the description of symptoms and their impact on visual acuity, it is imperative to use a tool that relies more on objective findings from ophthalmologic evaluations. The novel ocular adverse reaction severity grading scale developed by Amgen in collaboration with expert ophthalmologists, accounts for the anatomical regions impacted by ocular adverse reactions and anchors each severity grade to objective observable criteria from ophthalmologic evaluations. This grading scale is being used across the clinical development program for bemarituzumab to precisely characterize the ocular safety profile, enabling cross-specialty collaboration between oncologists and eye care providers to implement appropriate management strategies. This commentary article highlights the efforts led by Amgen in collaboration with regulatory, medical, and academic fields to develop tools that facilitate early recognition of adverse reactions and appropriate interventions for patient care.
靶向癌症疗法改变了癌症治疗的格局，但由于健康组织（包括眼部组织）中存在重叠的分子途径，这些疗法往往与脱靶药物不良反应相关。成纤维细胞生长因子受体（FGFRs）在眼睛的各个部位都有表达，可能会成为FGFR抑制剂（如厄达替尼、英菲格拉替尼和培米加替尼）的意外靶点，从而导致影响眼表和视网膜的眼部不良事件（AEs）。临床试验中的不良事件是根据美国国立癌症研究所（NCI）的不良事件通用术语标准（CTCAE）进行分级的，该标准可能无法完全捕捉到使用新兴疗法导致的眼部后遗症。由于CTCAE分级主要是通过对症状及其对视力的影响进行描述，因此必须使用一种更多依赖眼科评估客观结果的工具。安进公司与眼科专家合作开发的新型眼部不良反应严重程度分级量表，考虑了眼部不良反应所影响的解剖区域，并将每个严重程度等级与眼科评估的客观可观察标准相关联。该分级量表正在贝玛妥昔单抗的整个临床开发项目中使用，以精确描述眼部安全性概况，使肿瘤学家和眼科护理人员能够跨专业合作，实施适当的管理策略。这篇评论文章强调了安进公司与监管、医学和学术领域合作所做的努力，以开发有助于早期识别不良反应并为患者护理采取适当干预措施的工具。
