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LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY
BACKGROUND: RAS/RAF/MEK/ERK pathway activation is the primary driver for most pediatric low-grade gliomas (LGG). Binimetinib is an orally bioavailable MEK1/2 inhibitor found to have significant central nervous system penetration in a preclinical model. OBJECTIVE: The primary objective of this multi-...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715340/ http://dx.doi.org/10.1093/neuonc/noaa222.430 |
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author | Robison, Nathan Pauly, Jasmine Malvar, Jemily Gardner, Sharon Allen, Jeffrey MacDonald, Tobey Aguilera, Dolly Baxter, Patricia Bendel, Anne Kilburn, Lindsay Leary, Sarah Bowers, Daniel Dorris, Kathleen Gauvain, Karen Alva, Elizabeth Cohen, Kenneth Nazemi, Kellie Tan, Yi Juin Margol, Ashley Dhall, Girish Rosser, Tena Davidson, Tom Plant, Ashley Ullrich, Nicole Bandopadhayay, Pratiti Agar, Nathalie Ligon, Keith Sposto, Richard Wright, Karen Kieran, Mark |
author_facet | Robison, Nathan Pauly, Jasmine Malvar, Jemily Gardner, Sharon Allen, Jeffrey MacDonald, Tobey Aguilera, Dolly Baxter, Patricia Bendel, Anne Kilburn, Lindsay Leary, Sarah Bowers, Daniel Dorris, Kathleen Gauvain, Karen Alva, Elizabeth Cohen, Kenneth Nazemi, Kellie Tan, Yi Juin Margol, Ashley Dhall, Girish Rosser, Tena Davidson, Tom Plant, Ashley Ullrich, Nicole Bandopadhayay, Pratiti Agar, Nathalie Ligon, Keith Sposto, Richard Wright, Karen Kieran, Mark |
author_sort | Robison, Nathan |
collection | PubMed |
description | BACKGROUND: RAS/RAF/MEK/ERK pathway activation is the primary driver for most pediatric low-grade gliomas (LGG). Binimetinib is an orally bioavailable MEK1/2 inhibitor found to have significant central nervous system penetration in a preclinical model. OBJECTIVE: The primary objective of this multi-institutional open-label phase II study was to assess preliminary efficacy of binimetinib in progressive pediatric LGG. The study included strata for both neurofibromatosis type I (NF1) and non-NF1 associated tumors, as well as a target validation (surgical) stratum. NF1 and surgical strata remain open to enrollment and will be reported separately. METHODS: Children aged 1–18 years with previously treated recurrent or progressive LGG were eligible. The dose of binimetinib was 32 mg/m(2)/dose twice daily. Partial and minor responses were defined, respectively, as 50% and 25% decrease in maximal two-dimensional measurements. RESULTS: Fifty-seven eligible patients without NF1, median age 8 years, were enrolled and began treatment; 26 were female; 28 had documented KIAA1549-BRAF fusion. Eleven patients discontinued drug in the first year due to toxicity, and an additional 27 required dose reduction. The most common drug-attributable grade 3 toxicities included creatine kinase elevation (n=9 patients), rash (n=8), and truncal weakness (n=8). Truncal weakness improved or resolved with dose reduction or cessation. Grade 4 toxicities included creatine kinase elevation (n=2) and transient colitis (n=1). Of 44 patients with preliminary response data available, 22 (50%) showed a minor (n=7) or partial (n=15) response. CONCLUSION: Binimetinib is active, with manageable toxicities, in children without NF1 with progressive LGG. |
format | Online Article Text |
id | pubmed-7715340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77153402020-12-09 LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY Robison, Nathan Pauly, Jasmine Malvar, Jemily Gardner, Sharon Allen, Jeffrey MacDonald, Tobey Aguilera, Dolly Baxter, Patricia Bendel, Anne Kilburn, Lindsay Leary, Sarah Bowers, Daniel Dorris, Kathleen Gauvain, Karen Alva, Elizabeth Cohen, Kenneth Nazemi, Kellie Tan, Yi Juin Margol, Ashley Dhall, Girish Rosser, Tena Davidson, Tom Plant, Ashley Ullrich, Nicole Bandopadhayay, Pratiti Agar, Nathalie Ligon, Keith Sposto, Richard Wright, Karen Kieran, Mark Neuro Oncol Low Grade Glioma BACKGROUND: RAS/RAF/MEK/ERK pathway activation is the primary driver for most pediatric low-grade gliomas (LGG). Binimetinib is an orally bioavailable MEK1/2 inhibitor found to have significant central nervous system penetration in a preclinical model. OBJECTIVE: The primary objective of this multi-institutional open-label phase II study was to assess preliminary efficacy of binimetinib in progressive pediatric LGG. The study included strata for both neurofibromatosis type I (NF1) and non-NF1 associated tumors, as well as a target validation (surgical) stratum. NF1 and surgical strata remain open to enrollment and will be reported separately. METHODS: Children aged 1–18 years with previously treated recurrent or progressive LGG were eligible. The dose of binimetinib was 32 mg/m(2)/dose twice daily. Partial and minor responses were defined, respectively, as 50% and 25% decrease in maximal two-dimensional measurements. RESULTS: Fifty-seven eligible patients without NF1, median age 8 years, were enrolled and began treatment; 26 were female; 28 had documented KIAA1549-BRAF fusion. Eleven patients discontinued drug in the first year due to toxicity, and an additional 27 required dose reduction. The most common drug-attributable grade 3 toxicities included creatine kinase elevation (n=9 patients), rash (n=8), and truncal weakness (n=8). Truncal weakness improved or resolved with dose reduction or cessation. Grade 4 toxicities included creatine kinase elevation (n=2) and transient colitis (n=1). Of 44 patients with preliminary response data available, 22 (50%) showed a minor (n=7) or partial (n=15) response. CONCLUSION: Binimetinib is active, with manageable toxicities, in children without NF1 with progressive LGG. Oxford University Press 2020-12-04 /pmc/articles/PMC7715340/ http://dx.doi.org/10.1093/neuonc/noaa222.430 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Low Grade Glioma Robison, Nathan Pauly, Jasmine Malvar, Jemily Gardner, Sharon Allen, Jeffrey MacDonald, Tobey Aguilera, Dolly Baxter, Patricia Bendel, Anne Kilburn, Lindsay Leary, Sarah Bowers, Daniel Dorris, Kathleen Gauvain, Karen Alva, Elizabeth Cohen, Kenneth Nazemi, Kellie Tan, Yi Juin Margol, Ashley Dhall, Girish Rosser, Tena Davidson, Tom Plant, Ashley Ullrich, Nicole Bandopadhayay, Pratiti Agar, Nathalie Ligon, Keith Sposto, Richard Wright, Karen Kieran, Mark LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY |
title | LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY |
title_full | LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY |
title_fullStr | LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY |
title_full_unstemmed | LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY |
title_short | LGG-52. BINIMETINIB IN CHILDREN WITH PROGRESSIVE OR RECURRENT LOW-GRADE GLIOMA NOT ASSOCIATED WITH NEUROFIBROMATOSIS TYPE 1: INITIAL RESULTS FROM A MULTI-INSTITUTIONAL PHASE II STUDY |
title_sort | lgg-52. binimetinib in children with progressive or recurrent low-grade glioma not associated with neurofibromatosis type 1: initial results from a multi-institutional phase ii study |
topic | Low Grade Glioma |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715340/ http://dx.doi.org/10.1093/neuonc/noaa222.430 |
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