Precision oncology in pediatric brain tumors: Real world experience from a middle income country.

Abstract

e22015 Background: Despite the improvements in survival, treatment of recurrent/refractory (RR) central nervous system (CNS) tumors is challenging. Biologically targeted therapies (TT) offer a promising new option in neuro-oncology. This study aims to assess the safety and outcomes of TT in children and adolescents with RR CNS tumors in a single center in a middle income country and provide real-world experience. Methods: Medical records of children with RR CNS tumors treated between January 2021 and December 2024 with TT were retrospectively evaluated. TT were used with regulatory approval. Results: Twenty-two patients (11 female, 11 male) with RR CNS tumors, including 8 pediatric type diffuse high grade gliomas (HGG) [6 were diffuse midline gliomas (DMG)], 12 pediatric-type diffuse low-grade gliomas/circumscribed astrocytic gliomas (LGG) [10 hypothalamic optic gliomas (HOG), 6 of whom had NF1], 1 medulloblastoma, and 1 bilateral acoustic neuroma, received TT (alone or with chemotherapy). Four patients had H3K27m mutation, 1 EZH2 expression, 3 BRAF V600E mutation, 2 BRAF KIAA1549 fusion, 1 BCAS1-BRAF fusion, The median age at diagnosis was 6 years and 8.5 years at the start of TT. Agents used included dabrafenib+trametinib (3), trametinib(3), bevacizumab (17), nimotuzumab (5), everolimus (1),ONC201 (2), ONC206 (1). In addition to these patients, three patients (2 male, 1 female) with glial tumors (2 HGG, 1 LGG) who had the NTRK fusion and treated within an international trial have not been included in the present study. TT was administered for a median of 12 months. After the initiation of TT, 9 patients experienced progression after a median of 5 months, 3 patients had stable disease for a median of 26 months, 7 had partial response for a median of 12 months, 1 had a complete response for 4 months, and 2 maintained a continuing complete response for 22 and 26 months. Three patients had spinal/leptomeningeal metastasis, in two there was complete response in the metastasis to bevacuzimab containing regimen. In a patient with a second relapse of medulloblastoma there was complete response to nimotuzumab. Four patients (all with DMG) died after a median of 13.5 months, while 18 patients are alive at a median of 24 months from start of TT. The 2-year overall survival (OS) and progression-free survival (PFS) from diagnosis were 85.9% and 26.5%, respectively; the 2-year OS and PFS from the initiation of TT, were 78.4% and PFS 52%, respectively. Toxicities were manageable, with none requiring discontinuation of treatment Conclusions: Our experience with biologically targeted therapies in RR CNS tumors was promising with manageable toxicities. Further studies could explore TT in earlier treatment lines and/or as maintenance therapy.