Targeted Therapy

Therapeutically targetable somatic BRAF V600E variants are present in a small subset of patients with pediatric-type diffuse high-grade gliomas. Data from a nonrandomized retrospective study suggest that up-front inclusion of BRAF and/or MEK inhibitor therapy in place of chemotherapy may result in improved survival.[45][Level of evidence C2]

There is evidence that infants with group 1 hemispheric high-grade gliomas that have specific RTK-driven gene fusions are responsive to RTK-targeted therapeutics.[43,46] A subset analysis included 33 patients with NTRK fusion–positive central nervous system tumors who were treated with larotrectinib (included in two larger trials that enrolled children and adults with solid tumors and NTRK fusions).[47] The objective response rate was 30%, and 82% of patients with measurable disease had tumor shrinkage. The 12-month duration of response rate was 75%, the PFS rate was 56%, and the OS rate was 85%.[47] The role of RTK inhibitors in the up-front treatment of infants with pediatric-type high-grade glioma remains under study.