Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

IF 16.4 1区 医学 Q1 CLINICAL NEUROLOGY
Karsten Nysom, Lindsay B Kilburn, Sarah E S Leary, Daniel B Landi, Evelien de Vos-Kerkhof, Sébastien Perreault, Olaf Witt, David S Ziegler, Pablo Hernáiz Driever, Andrea T Franson, Patricia A Baxter, Nicholas S Whipple, Cassie Kline, Devorah Segal, Nada Jabado, Simon Bailey, Geoffrey McCowage, Jordan R Hansford, Dong-Anh Khuong-Quang, Nicholas G Gottardo, Timothy Hassall, Jung Woo Han, Michal Yalon Oren, Susan N Chi, Jiaheng Qiu, Daniel Da Costa, Sandya Govinda Raju, Peter Manley, Darren Hargrave
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引用次数: 0

Abstract

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG). In this post hoc analysis, anti-tumor activity and VA were analyzed in arm 1 patients with OPG. Anti-tumor activity was independently assessed per Response Assessment in Neuro-Oncology high-grade glioma (RANO-HGG), Response Assessment in Pediatric Neuro-Oncology-LGG (RAPNO) and RANO-LGG criteria. The data cutoff was June 5, 2023.

Results: Forty-two of 77 patients had OPGs; 35 of 42 had ≥2 VA assessments. The overall response rate in the OPG subgroup according to RANO-HGG, RAPNO and RANO-LGG criteria were 64%, 50%, and 55%, with clinical benefit rates 95%, 88%, and 90%, respectively. VA per patient was preserved for 80% of patients; 31% demonstrated improved VA; VA per eye was preserved in 87%, with 27% improving. The safety profile in the arm 1 OPG subgroup was similar to the overall FIREFLY-1 safety analysis set.

Conclusions: Tovorafenib demonstrated anti-tumor activity in relapsed/refractory BRAF-altered OPG across radiological assessment criteria and was generally well tolerated. Importantly, vision remained stable or improved in most patients.

FIREFLY-1试验中复发/难治性视通路胶质瘤患儿对II型RAF抑制剂托福拉非尼的放射学和视觉反应。
背景:视神经胶质瘤(OPGs)由于其解剖位置,很少能通过切除治愈。考虑到保留视觉功能的重要性,我们分析了II型RAF抑制剂tovorafenib在2期firefy -1试验中OPG亚组的放射学和视力(VA)结果。方法:FIREFLY-1研究tovorafenib (420 mg/m2,每周1次;braf改变的复发/难治性儿童低级别胶质瘤(pLGG)患者(最大600 mg)。在这项事后分析中,对1组OPG患者的抗肿瘤活性和VA进行了分析。根据神经肿瘤高级别胶质瘤反应评估(RANO-HGG)、儿科神经肿瘤反应评估(RAPNO)和RANO-LGG标准独立评估抗肿瘤活性。数据截止日期为2023年6月5日。结果:77例患者中42例发生OPGs;42人中有35人有≥2个VA评估。根据RANO-HGG、RAPNO和RANO-LGG标准,OPG亚组的总有效率分别为64%、50%和55%,临床获益率分别为95%、88%和90%。80%的患者保留了每位患者的VA;31%的VA改善;每只眼的VA保留率为87%,改善率为27%。1臂OPG亚组的安全性与整体FIREFLY-1安全性分析集相似。结论:Tovorafenib在复发/难治性braf改变的OPG中显示出抗肿瘤活性,并且总体耐受性良好。重要的是,大多数患者的视力保持稳定或有所改善。
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来源期刊
Neuro-oncology
Neuro-oncology 医学-临床神经学
CiteScore
27.20
自引率
6.30%
发文量
1434
审稿时长
3-8 weeks
期刊介绍: Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field. The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.
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