Tsukumo Yoshinori, Inoue Takao
Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences.
Gan To Kagaku Ryoho. 2024 Apr;51(4):368-377.
Companion diagnostics(CDx)are in vitro diagnostic products that are used to predict the efficacy and adverse effects of therapeutic drugs prior to administration, and are co-developed and co-approved with the therapeutic drugs in principle. In Japan, 40 CDx products have been approved by January 2024, and 39 products are used to determine if therapeutic drugs are applicable for cancer treatment. In the CDx products for cancer treatment, PCR, immunohistochemistry, or in situ hybridization is used to clarify the mutations(point mutations, insertions/deletions, fusions, etc.)in cancer-related genes or the expression levels of cancer-related molecules in the cancer tissues. The results of the analysis determine whether a particular therapeutic drug could be used or not for the treatment of the corresponding patient. Recently, several next-generation sequencing(NGS)-based CDx products have been approved and utilized for cancer treatment. The rise of NGS-based diagnostics has made it possible to comprehensively analyze mutations in many cancer-related genes in a single test and to determine whether each of several therapeutic drugs is applicable to the patient at once. On the other hand, with the increase in the number of CDx products, several regulatory issues have arisen, including an issue related to the co-development of CDx and a therapeutic drug and an issue related to the interchangeable use of CDx products that detect the same mutations of the cancer-related genes. The revision of CDx-related guidance is being considered in Japan and overseas in response to this situation.
伴随诊断（CDx）是一种体外诊断产品，用于在给药前预测治疗药物的疗效和不良反应，原则上与治疗药物共同开发和共同批准。在日本，截至2024年1月已有40种CDx产品获得批准，其中39种产品用于确定治疗药物是否适用于癌症治疗。在用于癌症治疗的CDx产品中，采用聚合酶链反应（PCR）、免疫组织化学或原位杂交等方法来明确癌症相关基因中的突变（点突变、插入/缺失、融合等）或癌症组织中癌症相关分子的表达水平。分析结果决定了特定治疗药物是否可用于相应患者的治疗。近年来，几种基于下一代测序（NGS）的CDx产品已获批准并用于癌症治疗。基于NGS的诊断技术的兴起使得在一次检测中全面分析多个癌症相关基因的突变并同时确定几种治疗药物中的每一种是否适用于该患者成为可能。另一方面，随着CDx产品数量的增加，出现了几个监管问题，包括与CDx和治疗药物共同开发相关的问题以及与检测癌症相关基因相同突变的CDx产品可互换使用相关的问题。针对这种情况，日本和海外正在考虑修订与CDx相关的指南。
