Dei-03. Compassionate Use of Novel and Targeted Therapies in Relapsed and Progressive Malignat Pediatric Brain Tumors: Experience of a Single Institution

BACKGROUND Off-label use of targeted therapy in pediatric Neuro Oncology is often offered to patients in the absence of available Clinical Trials specifically designed to this population. We present here six pediatric patients diagnosed with a malignant brain tumor who received compassionate treatment with targeted/novel therapy, alone or in combination, at disease progression or relapse, in a palliative setting. METHODS Retrospective chart review of patients diagnosed with a malignant brain tumor harboring a targeted molecular alteration, who received compassionate prescription of novel therapies not approved for the specific indication, and that were no eligible for a clinical trial. Patient demographics, dose of treatment delivered, tolerance, adverse effects, length of treatment, reason to discontinue the drug and survival rates were analyzed. RESULTS Four girls and two boys were identified; Median age at initiation of off-label drug: 4 years (3-17). Tumor type and targeted therapy delivered: DIPG H3 mutant (2), Diffuse Midline Glioma H3 and FGFR mutant (1), SHH-Medulloblastoma (1), ATRT (1), Diffusse Glioma EGFR and MET mutant (1). Off label drugs prescribed were ONC201, Erdafinitib, Sonidegib, Tazemetostat, and combination of crizotinib and erlotinib, respectively. Adverse events were mainly grade 1 and 2, however, 2/6 patients required hospital admission to manage adverse effects related to the experimental drug. One patient discontinued the drug due to side effects. All patients died of disease progression at a median of six months. CONCLUSIONS The anecdotical use of compassionate use of experimental drugs do not allow to gather clinical experience or to demonstrate a clinical benefit or impact in survival. Although the tolerance was generally good, the potential side effects caused by off-label drugs in a palliative population deserves a thorough individual assessment for its indication. Urgent need of targeted and novel therapies is warranted for pediatric children with malignant brain tumors.