Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition Journal Article

   


Authors: Nobre, L.; Zapotocky, M.; Ramaswamy, V.; Ryall, S.; Bennett, J.; Alderete, D.; Guill, J. B.; Baroni, L.; Bartels, U.; Bavle, A.; Bornhorst, M.; Boue, D. R.; Canete, A.; Chintagumpala, M.; Coven, S. L.; Cruz, O.; Dahiya, S.; Dirks, P.; Dunkel, I. J.; Eisenstat, D.; Conter, C. F.; Finch, E.; Finlay, J. L.; Frappaz, D.; Garre, M. L.; Gauvain, K.; Bechensteen, A. G.; Hansford, J. R.; Harting, I.; Hauser, P.; Hazrati, L. N.; Huang, A.; Injac, S. G.; Iurilli, V.; Karajannis, M.; Kaur, G.; Kyncl, M.; Krskova, L.; Laperriere, N.; Larouche, V.; Lassaletta, A.; Leary, S.; Lin, F.; Mascelli, S.; McKeown, T.; Milde, T.; La Madrid, A. M.; Morana, G.; Morse, H.; Mushtaq, N.; Osorio, D. S.; Packer, R.; Pavelka, Z.; Quiroga-Cantero, E.; Rutka, J.; Sabel, M.; Salgado, D.; Solano, P.; Sterba, J.; Su, J.; Sumerauer, D.; Taylor, M. D.; Toledano, H.; Tsang, D. S.; Fernandes, M. V.; van Landeghem, F.; van Tilburg, C. M.; Wilson, B.; Witt, O.; Zamecnik, J.; Bouffet, E.; Hawkins, C.; Tabori, U.
Article Title: Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition
Abstract: PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy (P, .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively (P = .02). CONCLUSION Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas. © 2020 by American Society of Clinical Oncology
Journal Title: JCO Precision Oncology
Volume: 4
ISSN: 2473-4284
Publisher: American Society of Clinical Oncology  
Date Published: 2020-05-20
Start Page: 561
End Page: 571
Language: English
DOI: 10.1200/po.19.00298
PROVIDER: scopus
PMCID: PMC7446502
PUBMED: 32923898
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85086464281&doi=10.1200%2fPO.19.00298&partnerID=40&md5=014549abcd1c3d49d1cddbb4ca54c072
Notes: Conference Paper -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Matthias Angelos Karajannis
    141 Karajannis
  2. Ira J Dunkel
    371 Dunkel
  3. Gurcharanjeet Kaur
    6 Kaur
Related MSK Work