Nysom, Karsten;
Kilburn, Lindsay B;
Leary, Sarah ES;
Landi, Daniel B;
de Vos-Kerkhof, Evelien;
Perreault, Sebastien;
Witt, Olaf;
... Hargrave, Darren; + view all
(2025)
Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.
Neuro-Oncology
, 27
(5)
10.1093/neuonc/noae274.
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Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsedrefractory optic pathway .pdf - Accepted Version Download (525kB) | Preview |
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 of 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.
| Type: | Article |
|---|---|
| Title: | Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/neuonc/noae274 |
| Publisher version: | https://doi.org/10.1093/neuonc/noae274 |
| Language: | English |
| Additional information: | © The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. Karsten Nysom , Lindsay B. Kilburn, Sarah E. S. Leary , Daniel B. Landi, Evelien de Vos-Kerkhof, Sébastien Perreault, OlafWitt, 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 , MichalYalon Oren, Susan N. Chi , Jiaheng Qiu, Daniel Da Costa, Sandya Govinda Raju, Peter Manley, and Darren Hargrave All author affiliations are listed at the end of the article Corresponding Author: Karsten Nysom, MD, PhD, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Section 5092, København 2100, Denmark (karsten.nysom@ regionh.dk). 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 of 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. Key Points • Tovorafenib may be an effective therapy for BRAF-altered optic pathway glioma. • Stable or improved vision per patient and per eye was seen in 80% of patients and 87% of eyes, respectively. • Preservation of vision is an important treatment outcome in optic pathway glioma. Low-grade glioma (LGG) is the most common central nervous system (CNS) tumor in children.1 Approximately one-third of pediatric (p)LGGs are located in the optic pathway/ hypothalamic region and are referred to as optic pathway gliomas (OPGs).2,3 While pLGGs located in the posterior fossa or the cerebral hemispheres are potentially curable by surgical Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/ refractory optic pathway glioma in the FIREFLY-1 trial This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https:// creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | BRAF, FIREFLY-1, optic pathway glioma, tovorafenib, visual acuity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10214532 |
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