{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:07:36Z","timestamp":1792786056875,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Day One Biopharmaceuticals, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>FIREFLY-1 investigated the efficacy (arm 1, n\u2005=\u200577), 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty-two of 77 patients had OPGs; 35 of 42 had \u22652 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noae274","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T07:36:55Z","timestamp":1734507415000},"page":"1341-1355","source":"Crossref","is-referenced-by-count":16,"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"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2935-0058","authenticated-orcid":false,"given":"Karsten","family":"Nysom","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet , Copenhagen, Capital Region of Denmark ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay B","family":"Kilburn","sequence":"additional","affiliation":[{"name":"Children\u2019s National Hospital , Washington, District of Columbia ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-6184","authenticated-orcid":false,"given":"Sarah E S","family":"Leary","sequence":"additional","affiliation":[{"name":"Cancer and Blood Disorders Center, Seattle Children\u2019s Hospital , Seattle, Washington ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B","family":"Landi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"de Vos-Kerkhof","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Perreault","sequence":"additional","affiliation":[{"name":"CHU Sainte-Justine, Universit\u00e9 de Montr\u00e9al , Montreal, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Witt","sequence":"additional","affiliation":[{"name":"National Center for Tumor Diseases (NCT) , Heidelberg ,","place":["Germany"]},{"name":"German Cancer Consortium (DKTK) , Heidelberg ,","place":["Germany"]},{"name":"Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) , Heidelberg ,","place":["Germany"]},{"name":"Hopp Children\u2019s Cancer Center Heidelberg (KiTZ) , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Ziegler","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, University of New South Wales , Sydney, New South Wales ,","place":["Australia"]},{"name":"Children\u2019s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales , Sydney, New South Wales ,","place":["Australia"]},{"name":"Kids Cancer Centre, Sydney Children\u2019s Hospital , Randwick, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Hern\u00e1iz Driever","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology\/Hematology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, German HIT-LOGGIC-Registry for LGG in Children and Adolescents, Pediatric Neurooncology Program , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea T","family":"Franson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, C.S. Mott Children\u2019s Hospital, University of Michigan Medical School , Ann Arbor, Michigan ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3703-8742","authenticated-orcid":false,"given":"Patricia A","family":"Baxter","sequence":"additional","affiliation":[{"name":"Texas Children\u2019s Cancer Center, Texas Children\u2019s Hospital, Baylor College of Medicine , Houston, Texas ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas S","family":"Whipple","sequence":"additional","affiliation":[{"name":"Primary Children\u2019s Hospital and University of Utah , Salt Lake City, Utah ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7765-7690","authenticated-orcid":false,"given":"Cassie","family":"Kline","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devorah","family":"Segal","sequence":"additional","affiliation":[{"name":"NYU Langone Health , New York, New York ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-3692","authenticated-orcid":false,"given":"Nada","family":"Jabado","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McGill University Health Centre (MUHC), The Montreal Children\u2019s Hospital (MCH) , Montr\u00e9al, Quebec ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Bailey","sequence":"additional","affiliation":[{"name":"Great North Children\u2019s Hospital and Newcastle University Centre for Cancer , Newcastle-upon-Tyne ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"McCowage","sequence":"additional","affiliation":[{"name":"Sydney Children\u2019s Hospitals Network , Westmead, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan R","family":"Hansford","sequence":"additional","affiliation":[{"name":"South Australian Immunogenomics Cancer Institute, University of Adelaide , Adelaide,","place":["Australia"]},{"name":"South Australia Health and Medical Research Institute , Adelaide, South Australia ,","place":["Australia"]},{"name":"Michael Rice Centre for Hematology and Oncology, Women\u2019s and Children\u2019s Hospital , Adelaide, South Australia ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Anh","family":"Khuong-Quang","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Centre, The Royal Children\u2019s Hospital Melbourne , Melbourne, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas G","family":"Gottardo","sequence":"additional","affiliation":[{"name":"Brain Tumor Research Program, Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia , Perth, Washington ,","place":["Australia"]},{"name":"Department of Pediatric and Adolescent Oncology and Hematology, Perth Children\u2019s Hospital , Perth, Western Australia ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Hassall","sequence":"additional","affiliation":[{"name":"Children\u2019s Health Queensland Hospital and Health Service , South Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8936-1205","authenticated-orcid":false,"given":"Jung Woo","family":"Han","sequence":"additional","affiliation":[{"name":"Severance Hospital, Yonsei University Health System , Seoul ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Yalon Oren","sequence":"additional","affiliation":[{"name":"Pediatric Hemato-Oncology Department, Sheba Medical Center , Ramat Gan, Tel Aviv District ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7753-878X","authenticated-orcid":false,"given":"Susan N","family":"Chi","sequence":"additional","affiliation":[{"name":"Pediatric Neuro-Oncology, Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaheng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Day One Biopharmaceuticals , Brisbane, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Da Costa","sequence":"additional","affiliation":[{"name":"Day One Biopharmaceuticals , Brisbane, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandya","family":"Govinda Raju","sequence":"additional","affiliation":[{"name":"Day One Biopharmaceuticals , Brisbane, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Manley","sequence":"additional","affiliation":[{"name":"Day One Biopharmaceuticals , Brisbane, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Hargrave","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"issue":"1","key":"2025062421074835000_CIT0001","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/neuonc\/noad195","article-title":"Pediatric low-grade glioma: state-of-the-art and ongoing challenges","volume":"26","author":"Fangusaro","year":"2024","journal-title":"Neuro Oncol."},{"key":"2025062421074835000_CIT0002","doi-asserted-by":"crossref","first-page":"884250","DOI":"10.3389\/fsurg.2022.884250","article-title":"Neurosurgery for optic pathway glioma: optimizing multidisciplinary management","volume":"9","author":"Samples","year":"2022","journal-title":"Front Surg."},{"key":"2025062421074835000_CIT0003","doi-asserted-by":"crossref","first-page":"1038937","DOI":"10.3389\/fped.2023.1038937","article-title":"A new era for optic pathway glioma: a developmental brain tumor with life-long health 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