LGG-07. TARGETED THERAPY IN PEDIATRIC LOW-GRADE GLIOMAS; REAL WORLD DATA IN THE CONTEXT OF CONVENTIONAL TREATMENT MODALITIES

Progressive inoperable pediatric low-grade gliomas (pLGG) are challenging and chemotherapy provides unsatisfactory long-term disease control. Majority of pLGGs harbor oncogenic MAPK pathway alterations. BRAF and MEK inhibitors were developed and available data suggest possible benefit in pLGG patients. Therefore, we aimed to evaluate efficacy and toxicity of dabrafenib in BRAF-V600E positive pLGG and trametinib in KIAA1549::BRAF fused or NF1-associated pLGGs. Retrospective review of patients with molecularly profiled pLGGs treated with MAPK inhibitors at our institutions was performed. Response to targeted therapies was evaluated using RAPNO criteria and volumetric analysis. Twenty-six patients were eligible for this study because they had either BRAF-V600E pLGG treated with dabrafenib (n=11) or KIAA1549::BRAF fused/NF1-associated pLGG treated with trametinib (n=15) outside clinical trials. Patients received targeted therapy because of radiological progression (n=18), clinical deterioration (n=2) or as an upfront approach (n=6). Overall response rate (ORR) of the whole cohort using RAPNO criteria was 46.1% (12/26). There was a discordance observed between RAPNO bidimensional and manual volumetric analysis in 7 patients (26.9%). Progression free survival (PFS) at 2 years for the whole evaluated cohort was 78.5%(95 CI, 63.2 to 97.4%). ORR of patients with BRAF-V600E pLGG was 64% (median time to response 2.6 months). Out of fifteen patients treated with trametinib, 33% achieved partial response (median time to response 6.6 months). In total, 6 patients experienced progression on therapy. Six patients were treated with vinca alkaloids and trametinib with no additional toxicity. All 15 patients experienced trametinib-related adverse event, grade III was reported in 6 (40%) of them. Altogether 11 patients (73%) required dose reductions or treatment interruptions. MAPK inhibitors represent novel treatment modality in pLGG patients with clinical benefit in proportion of patients. Nevertheless, patients may experience progression on therapy requiring further management.