Futibatinib, an investigational agent for the treatment of intrahepatic cholangiocarcinoma: evidence to date and future perspectives
Futibatinib, an investigational agent for the treatment of intrahepatic cholangiocarcinoma: evidence to date and future perspectives
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DOI：
10.1080/13543784.2021.1837774
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发表时间：
2020-10-25
影响因子：
6.1
通讯作者：
Brandi, Giovanni
中科院分区：
文献类型：
--
作者：
Rizzo, Alessandro;Ricci, Angela Dalia;Brandi, Giovanni
胆道癌（btc）是一种预后不良的恶性肿瘤，通常分为肝内胆管癌（iCCA）、肝外胆管癌、胆囊癌和壶腹癌。在过去的几年中，在iCCA患者中发现了新的治疗靶点，包括成纤维细胞生长因子受体（FGFR）畸变；因此，目前正在开发几种FGFR抑制剂，其中一些已经在难治性iCCA的I期和II期试验中显示出有趣的疗效和足够的安全性。本综述概述了FGFR2靶向治疗在iCCA中的现状，特别关注高选择性不可逆泛fgfr拮抗剂futibatinib （TAS-120）的作用机制和临床发展。根据FOENIX-CCA2试验的中期分析，其结果已在2020年美国临床肿瘤学会（ASCO）年会上公布，福替替尼可为先前治疗过的伴有FGFR2基因融合或其他重排的iCCA患者带来有意义的益处。由于其具有前景和持久的活性，福替替尼有可能成为治疗含有FGFR2异常的icca的一种新的治疗选择。需要进一步的研究来证实该研究分子的有效性。
IntroductionBiliary tract cancers (BTCs) are poor prognosis malignancies usually classified in intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer. In the last few years, novel treatment targets have been identified in iCCA patients, including fibroblast growth factor receptor (FGFR) aberrations; thus, several FGFR inhibitors are currently being developed, some of which have already suggested interesting efficacy and adequate safety in phase I and phase II trials regarding refractory iCCA.Areas coveredThis review provides an overview regarding the current scenario of FGFR2 targeted therapies in iCCA, especially focusing on the mechanism of action and clinical development of futibatinib (TAS-120), a highly selective irreversible pan-FGFR antagonist. According to the interim analysis of the FOENIX-CCA2 trial, whose results have been presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, futibatinib could lead to meaningful benefit in patients affected by previously treated iCCA with FGFR2 gene fusions or other rearrangements.Expert opinionBecause of its promising and durable activity, futibatinib has the potential to become a novel therapeutic option in the treatment of iCCAs harboring FGFR2 aberrations. Further studies are warranted to confirm the efficacy of this investigational molecule.