(220) Single-Center Pediatric Experience With BRAF-and/orMEK-Inhibitors for Treatment of Pediatric Glioma

Poster Abstract:

Background:
The treatment of pediatric gliomas has historically consisted of conventional chemotherapy and/or radiation which leads to significant morbidity. As compared to wild type disease, BRAF-mutated pediatric gliomas often exhibit a poor response to standard chemotherapy and are associated with lower progression free survival and overall survival. The targetable mutation and less significant toxicities associated with oral oncolytics has led to a desire to move away from conventional chemotherapy. For the past several years, the Memorial Sloan Kettering Kids Neuro-Oncology Service has been utilizing off-label dabrafenib and trametinib, in combination as well as monotherapy, for a variety of pediatric gliomas. The aim of this study was to describe the real-world tolerability of BRAF-and/or MEK-inhibitors for the treatment of pediatric gliomas.

Objectives:
The primary objective was to describe the discontinuation rates and side effect profiles of BRAF- and/or MEK-inhibitors in pediatric patients prescribed treatment for a glioma. The secondary objectives included assessing the differences in side effect profiles between BRAF- and MEK-inhibitors, assessing the toxicities that warranted a switch to a different BRAF- and/or MEK-inhibitor, and describing tumor response with BRAF- and/or MEK-inhibitor therapy.

Methods:
This study was approved under the Institutional Review Board at Memorial Sloan Kettering Cancer Center. A retrospective chart review was conducted to describe the use of BRAF-and MEK-inhibitors in pediatric patients 1 year of age to less than 18 years of age with any grade glioma. The following baseline & treatment data was collected: cancer diagnosis, treatment regimens received to date, tumor genetics/pathology, ordered dose, duration of treatment, reported adherence, and manipulation of dosage form for the BRAF- and/or MEK-inhibitors. For each patient that received a BRAF-and/or MEK-inhibitor if the dose was reduced, held, or discontinued, the CTCAE grade and management of toxicities will also be collected. Descriptive statistics will be used to describe the incidence of adverse events in the study population, as well as the rate of treatment discontinuation.

Results:
Between May 1, 2013, and June 30, 2023, 32 patients (Median age: 8 years, range: 1 to 17 years) diagnosed with a pediatric glioma that received a BRAF- and/or MEK-inhibitor were reviewed. Results pending.

Conclusion:
Results pending

References (must also be included in final poster): 1. 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. 2023;41(3):664-674.
2. 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. 2019;25(24):7303-7311.
3. Selt F, van Tilburg CM, Bison B, et al. Response to trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol. 2020 Sep;149(3):499-510.
4. Product information TAFINLAR® (daBRAFenib). GlaxoSmithKline. Research Triangle Park, NC. June 2022
5. Product information MEKINIST (TRAMETinib). GlaxoSmithKline. Research Triangle Park, NC. June 2022
6. Hanzlik E, Archambault B, El-Dairi M, et al. Use of trametinib in children and young adults with progressive low-grade glioma and glioneuronal tumors. J Pediatr Hematol Oncol. 2023 May 1;45(4):e464-e470.