68
Views
0
CrossRef citations to date
0
Altmetric
Review

A critical review of RAF inhibitors in BRAF-mutated glioma treatment

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Received 18 Mar 2024, Accepted 13 May 2024, Published online: 03 Jun 2024

References

  • Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2014–2018. Neuro-Oncol. 2021;23(2 Suppl. 12):iii1–iii105. doi:10.1093/neuonc/noab200
  • Dn L, P A, W P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro-Oncol. 2021;23(8):1231–1251. doi:10.1093/neuonc/noab106
  • Chen R, Smith-Cohn M, Cohen AL, Colman H. Glioma subclassifications and their clinical significance. Neurother J Am Soc Exp Neurother. 2017;14(2):284–297. doi:10.1007/s13311-017-0519-x
  • Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–954. doi:10.1038/nature00766
  • Ghanem P, Fatteh M, Kamson DO, et al. Druggable genomic landscapes of high-grade gliomas. Front Med. 2023;10:1254955. doi:10.3389/fmed.2023.1254955
  • Ullah R, Yin Q, Snell AH, Wan L. RAF-MEK-ERK pathway in cancer evolution and treatment. Semin Cancer Biol. 2022;85:123–154. doi:10.1016/j.semcancer.2021.05.010
  • Degirmenci U, Wang M, Hu J. Targeting aberrant RAS/RAF/MEK/ERK signaling for cancer therapy. Cells. 2020;9(1):198. doi:10.3390/cells9010198
  • Yao Z, Yaeger R, Rodrik-Outmezguine VS, et al. Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS. Nature. 2017;548(7666):234–238. doi:10.1038/nature23291
  • Dankner M, Rose AAN, Rajkumar S, Siegel PM, Watson IR. Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations. Oncogene. 2018;37(24):3183–3199. doi:10.1038/s41388-018-0171-x
  • Yao Z, Torres NM, Tao A, et al. BRAF mutants evade ERK-dependent feedback by different mechanisms that determine their sensitivity to pharmacologic inhibition. Cancer Cell. 2015;28(3):370–383. doi:10.1016/j.ccell.2015.08.001
  • Wen PY, Macdonald DR, Reardon DA, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(11):1963–1972. doi:10.1200/JCO.2009.26.3541
  • Wen PY, Chang SM, Van den Bent MJ, Vogelbaum MA, Macdonald DR, Lee EQ. Response assessment in neuro-oncology clinical trials. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(21):2439–2449. doi:10.1200/JCO.2017.72.7511
  • Fangusaro J, Witt O, Hernáiz Driever P, et al. Response assessment in paediatric low-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. Lancet Oncol. 2020;21(6):e305–e316. doi:10.1016/S1470-2045(20)30064-4
  • Behling F, Barrantes-Freer A, Skardelly M, et al. Frequency of BRAF V600E mutations in 969 central nervous system neoplasms. Diagn Pathol. 2016;11(1):55. doi:10.1186/s13000-016-0506-2
  • Kleinschmidt-DeMasters BK, Aisner DL, Foreman NK. BRAF VE1 immunoreactivity patterns in epithelioid glioblastomas positive for BRAF V600E mutation. Am Surg Pathol. 2015;39(4):528–540. doi:10.1097/PAS.0000000000000363
  • Koh HY, Kim SH, Jang J, et al. BRAF somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors. Nat Med. 2018;24(11):1662–1668. doi:10.1038/s41591-018-0172-x
  • Sun Y, Alberta JA, Pilarz C, et al. A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas. Neuro-Oncol. 2017;19(6):774–785. doi:10.1093/neuonc/now261
  • Tkacik E, Li K, Gonzalez-Del Pino G, et al. Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib. J Biol Chem. 2023;299(5):104634. doi:10.1016/j.jbc.2023.104634
  • Jain P, Fierst TM, Han HJ, et al. CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles. Oncogene. 2017;36(45):6348–6358. doi:10.1038/onc.2017.276
  • W H, LB J, Ba W, et al. Population pharmacokinetics of vemurafenib in children with recurrent/refractory BRAF gene V600E-mutant astrocytomas. J Clin Pharmacol. 2020;60(9):1209–1219. doi:10.1002/jcph.1617
  • Nicolaides T, Nazemi KJ, Crawford J, et al. Phase I study of vemurafenib in children with recurrent or progressive BRAFV600E mutant brain tumors: Pacific Pediatric Neuro-Oncology Consortium study (PNOC-002). Oncotarget. 2020;11(21):1942–1952. doi:10.18632/oncotarget.27600
  • Crocco M, Verrico A, Milanaccio C, et al. Dyslipidemia in children treated with a BRAF inhibitor for low-grade gliomas: a new side effect? Cancers. 2022;14(11):2693. doi:10.3390/cancers14112693
  • Kieran MW, Geoerger B, Dunkel IJ, et al. A Phase I and pharmacokinetic study of oral dabrafenib in children and adolescent patients with recurrent or refractory BRAF V600 mutation-positive solid tumors. Clin Cancer Res Off J Am Assoc Cancer Res. 2019;25(24):7294–7302. doi:10.1158/1078-0432.CCR-17-3572
  • Hargrave DR, Bouffet E, Tabori U, et al. Efficacy and safety of dabrafenib in pediatric patients with BRAF V600 mutation-positive relapsed or refractory low-grade glioma: results from a Phase I/IIa study. Clin Cancer Res Off J Am Assoc Cancer Res. 2019;25(24):7303–7311. doi:10.1158/1078-0432.CCR-19-2177
  • Bouffet E, Geoerger B, Moertel C, et al. Efficacy and safety of trametinib monotherapy or in combination with dabrafenib in pediatric BRAF V600-mutant low-grade glioma. J Clin Oncol Off J Am Soc Clin Oncol. 2023;41(3):664–674. doi:10.1200/JCO.22.01000
  • Bouffet E, Hansford JR, Garrè ML, et al. Dabrafenib plus trametinib in pediatric glioma with BRAF V600 mutations. N Engl J Med. 2023;389(12):1108–1120. doi:10.1056/NEJMoa2303815
  • Tsai JW, Choi JJ, Ouaalam H, et al. Integrated response analysis of pediatric low-grade gliomas during and after targeted therapy treatment. Neuro-Oncol Adv. 2023;5(1):vdac182. doi:10.1093/noajnl/vdac182
  • Kilburn LB, Khuong-Quang DA, Hansford JR, et al. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the Phase II FIREFLY-1 trial. Nat Med. Published online November 17, 2023. doi:10.1038/s41591-023-02668-y
  • Wright K, Kline C, Abdelbaki M, et al. CTNI-53. PNOC014: Phase IB study results Of DAY101(TOVORAFENIB) for children with low-grade gliomas (LGGS) and other RAS/RAF/MEK/ERK pathway-activated tumors. Neuro-Oncol. 2022;24(Suppl. 7):vii84. doi:10.1093/neuonc/noac209.318
  • van Tilburg CM, Kilburn LB, Perreault S, et al. LOGGIC/FIREFLY-2: a Phase III, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration. BMC Cancer. 2024;24:147. doi:10.1186/s12885-024-11820-x
  • Day One Biopharmaceuticals, Inc.. LOGGIC/FIREFLY-2: A Phase III, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy. Clinicaltrials.gov 2024. Accessed January 1, 2024. https://clinicaltrials.gov/study/NCT05566795
  • FDA Accepts NDA for Tovorafenib in Pediatric Low-Grade Glioma. Target. Oncol. Published October 30, 2023. Accessed January 18, 2024. https://www.targetedonc.com/view/fda-accepts-nda-for-tovorafenib-in-pediatric-low-grade-glioma
  • Hargrave DR, Terashima K, Hara J, et al. Phase II trial of dabrafenib plus trametinib in relapsed/refractory BRAF V600-mutant pediatric high-grade glioma. J Clin Oncol Off J Am Soc Clin Oncol. 2023;41(33):5174–5183. doi:10.1200/JCO.23.00558
  • Kaley T, Touat M, Subbiah V, et al. BRAF inhibition in BRAFV600-mutant gliomas: results from the VE-BASKET study. J Clin Oncol Off J Am Soc Clin Oncol. 2018;36(35):3477–3484. doi:10.1200/JCO.2018.78.9990
  • Subbiah V, Puzanov I, Blay JY, et al. Pan-cancer efficacy of vemurafenib in BRAFV600-MUTANT non-melanoma cancers. Cancer Discov. 2020;10(5):657–663. doi:10.1158/2159-8290.CD-19-1265
  • Blay JY, Cropet C, Mansard S, et al. Long term activity of vemurafenib in cancers with BRAF mutations: the ACSE basket study for advanced cancers other than BRAFV600-mutated melanoma. ESMO Open. 2023;8(6):102038. doi:10.1016/j.esmoop.2023.102038
  • Subbiah V, Sen S, Hess KR, et al. Phase I Study of the BRAF inhibitor vemurafenib in combination with the mammalian target of rapamycin inhibitor everolimus in patients with BRAF-mutated malignancies. JCO Precis Oncol. 2018;2:PO.18.00189. doi:10.1200/PO.18.00189
  • Py W A S, van den B M, et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, Phase II, basket trial. Lancet Oncol. 2022;23(1). doi:10.1016/S1470-2045(21)00578-7
  • Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the Phase II ROAR trial. Nat Med. 2023;29(5):1103–1112. doi:10.1038/s41591-023-02321-8
  • Berzero G, Bellu L, Baldini C, et al. Sustained tumor control with MAPK inhibition in BRAF V600-mutant adult glial and glioneuronal tumors. Neurology 2021;97(7):e673–e683. doi:10.1212/WNL.0000000000012330
  • Rasco DW, Medina T, Corrie P, et al. Phase I study of the pan-RAF inhibitor tovorafenib in patients with advanced solid tumors followed by dose expansion in patients with metastatic melanoma. Cancer Chemother Pharmacol. 2023;92(1):15–28. doi:10.1007/s00280-023-04544-5
  • Sievert AJ, Lang SS, Boucher KL, et al. Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas. Proc Natl Acad Sci USA. 2013;110(15):5957–5962. doi:10.1073/pnas.1219232110
  • Abuali I, Lee CS, Seetharamu N. A narrative review of the management of BRAF non-V600E mutated metastatic non-small cell lung cancer. Precis Cancer Med. 2022;5(0):13. doi:10.21037/pcm-21-49
  • Gampa G, Kim M, Mohammad AS, et al. Brain distribution and active efflux of three panRAF inhibitors: considerations in the treatment of melanoma brain metastases. J Pharmacol Exp Ther. 2019;368(3):446–461. doi:10.1124/jpet.118.253708
  • Kelly AM, Berry MR, Tasker SZ, McKee SA, Fan TM, Hergenrother PJ. Target-agnostic P-glycoprotein assessment yields strategies to evade efflux, leading to a BRAF inhibitor with intracranial efficacy. J Am Chem Soc. 2022;144(27):12367–12380. doi:10.1021/jacs.2c03944
  • Corrie P, Meyer N, Berardi R, et al. Comparative efficacy and safety of targeted therapies for BRAF-mutant unresectable or metastatic melanoma: results from a systematic literature review and a network meta-analysis. Cancer Treat Rev. 2022;110:102463. doi:10.1016/j.ctrv.2022.102463
  • Stinchcombe TE. Encorafenib and binimetinib: a new treatment option for BRAFV600E-mutant non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2023;41(21):3679–3681. doi:10.1200/JCO.23.00983
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. A Phase II study of binimetinib in combination with encorafenib in adults with recurrent BRAF V600-mutated high-grade astrocytoma or other primary brain tumor. Clinicaltrials.gov 2022. Accessed January 1, 2024. https://clinicaltrials.gov/study/NCT03973918
  • Schreck KC, Strowd RE, Nabors LB, et al. Response rate and molecular correlates to encorafenib and binimetinib in BRAF-V600E mutant high-grade glioma. Clin Cancer Res off J Am Assoc Cancer Res. Published online March 6, 2024. doi:10.1158/1078-0432.CCR-23-3241
  • Offer K, McGuire MT, Song K, et al. Activity of type II RAF inhibitor Tovorafenib in a pediatric patient with a recurrent spindle cell sarcoma harboring a novel SNX8-BRAF gene fusion. JCO Precis Oncol. 2023;7:e2300065. doi:10.1200/PO.23.00065
  • Suzuki R, Kitamura Y, Nakamura Y, et al. Anti-tumor activities of the new oral pan-RAF inhibitor, TAK-580, used as monotherapy or in combination with novel agents in multiple myeloma. Oncotarget. 2020;11(44):3984–3997. doi:10.18632/oncotarget.27775
  • Karajannis MA, Legault G, Fisher MJ, et al. Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas. Neuro-Oncol. 2014;16(10):1408–1416. doi:10.1093/neuonc/nou059
  • Picca A, Guyon D, Santonocito OS, et al. Innovating strategies and tailored approaches in neuro-oncology. Cancers. 2022;14(5):1124. doi:10.3390/cancers14051124
  • Santangelo A, Rossato M, Lombardi G, et al. A molecular signature associated with prolonged survival in glioblastoma patients treated with regorafenib. Neuro-Oncol. 2021;23(2):264–276. doi:10.1093/neuonc/noaa156
  • Northcott PA, Pfister SM, Jones DTW. Next-generation (epi)genetic drivers of childhood brain tumours and the outlook for targeted therapies. Lancet Oncol. 2015;16(6):e293–302. doi:10.1016/S1470-2045(14)71206-9
  • Wisoff JH, Sanford RA, Heier LA, et al. Primary neurosurgery for pediatric low-grade gliomas: a prospective multi-institutional study from the Children's Oncology Group. Neurosurgery. 2011;68(6):1548–1554; discussion 1554–1555. doi:10.1227/NEU.0b013e318214a66e
  • PDQ Pediatric Treatment Editorial Board. Childhood Astrocytomas, Other Gliomas, and Glioneuronal/Neuronal Tumors Treatment (PDQ®): Health Professional Version. In: PDQ Cancer Information Summaries. National Cancer Institute (US); 2002. Accessed May 10, 2024. http://www.ncbi.nlm.nih.gov/books/NBK65944/
  • Krishnatry R, Zhukova N, Guerreiro Stucklin AS, et al. Clinical and treatment factors determining long-term outcomes for adult survivors of childhood low-grade glioma: a population-based study. Cancer. 2016;122(8):1261–1269. doi:10.1002/cncr.29907
  • Armstrong GT, Conklin HM, Huang S, et al. Survival and long-term health and cognitive outcomes after low-grade glioma. Neuro-Oncol. 2011;13(2):223–234. doi:10.1093/neuonc/noq178
  • Fernando D, Ahmed AU, Williams BRG. Therapeutically targeting the unique disease landscape of pediatric high-grade gliomas. Front Oncol. 2024;14:1347694. doi:10.3389/fonc.2024.1347694

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.