Type II RAF inhibitor tovorafenib for the treatment of pediatric low-grade glioma.

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Tianqiao Zhang, Bo Xu, Fan Tang, Zunbo He, Jiecan Zhou
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引用次数: 0

Abstract

Introduction: Pediatric low-grade glioma (pLGG) is the most prevalent childhood brain tumor group, currently regarded as a chronic disease. On 23 April 2024, the U.S. FDA approved a new type II RAF inhibitor, tovorafenib (OJEMDATM), previously known as DAY101, for the treatment of patients aged 6 months and older with relapsed or refractory (R/R) pLGG harboring a BRAF fusion or rearrangement, or BRAF V600E mutation.

Areas covered: This article aims to review the pharmacological properties of tovorafenib and evaluate its efficacy and safety in the treatment of R/R pLGG. We conducted a systematic search of PubMed and Web of Science databases for English-language publications related to tovorafenib, including journal articles and conference abstracts, up through 20 August 2024.

Expert opinion: As the first and only FDA-approved medicine for children with BRAF fusions or rearrangements, which are the most common molecular alteration in pLGG, tovorafenib shows superior central nervous system penetration without the paradoxical activation of the MAPK pathway reported for type I BRAF inhibitors. Phase 1 and the pivotal phase 2 trials have demonstrated that tovorafenib monotherapy is generally well-tolerated and exhibits encouraging signs of meaningful, rapid and sustained clinical activity in children and young adults with BRAF-altered pLGG.

治疗小儿低级别胶质瘤的 II 型 RAF 抑制剂托伐非尼。
简介小儿低级别胶质瘤(pLGG)是发病率最高的儿童脑肿瘤,目前被视为一种慢性疾病。2024 年 4 月 23 日,美国 FDA 批准了一种新型 II 型 RAF 抑制剂--托伐非尼(OJEMDATM)(之前名为 DAY101),用于治疗年龄在 6 个月及以上、携带 BRAF 融合或重排或 BRAF V600E 突变的复发或难治性(R/R)pLGG 患者:本文旨在回顾托伐非尼的药理特性,并评估其治疗R/R pLGG的有效性和安全性。我们在PubMed和Web of Science数据库中系统检索了截至2024年8月20日与沃拉非尼相关的英文出版物,包括期刊论文和会议摘要:作为首个也是唯一一个获得FDA批准的治疗儿童BRAF融合或重排(pLGG中最常见的分子改变)的药物,tovorafenib显示出卓越的中枢神经系统穿透力,而不会出现I型BRAF抑制剂所报道的MAPK通路激活的矛盾现象。1 期和关键的 2 期试验表明,托伐非尼单药治疗的耐受性普遍良好,而且在患有 BRAF 改变的 pLGG 的儿童和年轻成人中显示出令人鼓舞的有意义、快速和持续的临床活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Expert Review of Clinical Pharmacology
Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.30
自引率
2.30%
发文量
127
期刊介绍: Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.
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