Treatment Landscape

With no formal guidelines, managing pLGG remains a challenge1

Ayiden, lives with pLGG.
Lives for basketball.

Depending on the location of the tumor, surgery is the preferred treatment choice for patients with pediatric low-grade glioma (pLGG). After gross total resection, prognosis is favorable, and initial adjuvant therapy is undesirable. This outcome is often achievable for superficial lesions.1,2

However, surgery is not always feasible for deep-seated or highly infiltrative tumors. If a gross total resection is not obtained or recommended, progression may be treated with additional surgery and subsequent adjuvant therapy.1,2

About 80% of incompletely resected tumors progress and require at least one line of adjuvant therapy.

of incompletely resected tumors progress and require at least one line of adjuvant therapy.3

Carboplatin-based chemotherapy is typically used postsurgery4

Common chemotherapy regimens in newly diagnosed pLGG are associated with 3-year PFS rates between 50-80%

of common chemotherapy regimens in newly diagnosed pLGG are associated with 3-year PFS rates between 50-80%.4

However, despite its established use, toxicity and tolerability issues with chemotherapy continue to be a concern for infants and young children.5

Treatment options for progressive/recurrent pLGG are limited

  • Lack of formal guidelines leaves patients without standardized treatment options upon progression or recurrence2

  • Most therapies used today have not been FDA-approved for pLGG6⁠‐⁠10

  • There are limited therapies available to treat across BRAF alterations in pLGG2

Advances in our understanding suggest the need for novel therapies to treat pLGG.

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Targeting BRAF

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References: 1. Ryall S, Tabori U, Hawkins C. Pediatric low-grade glioma in the era of molecular diagnostics. Acta Neuropathol Commun. 2020;8(1):30. doi:10.1186/s40478-020-00902-z 2. Collins KL, Pollack IF. Pediatric low-grade gliomas. Cancers (Basel). 2020;12(5):1152.4. doi:10.3390/cancers12051152 3. Selt F, van Tilburg CM, Bison B, et al. Response to trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol. 2020;149(3):499-510. doi:10.1007/s11060-020-03640-3 4. de Blank P, Bandopadhayay P, Haas-Kogan D, Fouladi M, Fangusaro J. Management of pediatric low-grade glioma. Curr Opin Pediatr. 2019;31(1):21-27. doi:10.1097/MOP.0000000000000717 5. Otth M, Wyss J, Scheinemann K. Long-term follow-up of pediatric CNS tumor survivors—a selection of relevant long-term issues. Children (Basel). 2020;9(4):447. doi:10.3390/children9040447 6. Schreck KC, Grossman SA, Pratilas CA. BRAF mutations and the utility of RAF and MEK inhibitors in primary brain tumors. Cancers (Basel). 2019;11(9):1262. doi:10.3390/cancers11091262 7. Tafinlar® [Package Insert]. East Hanover, NJ; Novartis Pharmaceuticals Corporation; 2022. 8. Braftovi® [Package Insert]. Boulder, CO: Array BioPharma, Inc.; 2022. 9. Koselugo® [Package Insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 10. Zelboraf® [Package Insert]. South San Francisco, CA: Genentech, Inc.; 2020. 11. Yaeger R, Corcoran RB. Targeting alterations in the RAF-MEK pathway. Cancer Discov. 2019;9(3):329-341. doi:10.1158/2159-8290.CD-18-1321 12. Holderfield M, Nagel TE, Stuart DD. Mechanism and consequences of RAF kinase activation by small-molecule inhibitors. Br J Cancer. 2014;111(4):640-645. doi:10.1038/bjc.2014.139 13. Wright K, Krzykwa E, Greenspan L, et al. EPCT-01 Phase I study of DAY101 (TAK580) in children and young adults with radiographically recurrent or progressive low-grade glioma (LGG). Neuro Oncol. 2020;22(Suppl 3):iii304. doi:10.1093/neuonc/noaa222.126 14. Drilon AE, Liu H, Wu F. Tumor-agnostic precision immuno-oncology and somatic targeting rationale for you (TAPISTRY): a novel platform umbrella trial. J Clin Oncol. 2021;39:15_suppl. doi:10.1200/JCO.2021.39.15_suppl.TPS3154 15. 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 16. 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 17. Heitzer AM, Raghubar K, Ris MD, et al. Neuropsychological functioning following surgery for pediatric low-grade glioma: a prospective longitudinal study. J Neurosurg Pediatr. 2019;1-9. doi:10.3171/2019.9.PEDS19357 18. Shortman RI, Beringer A, Penn A, Malson H, Lowis SP, Sharples PM. The experience of mothers caring for a child with a brain tumour. 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