Novel Pharmacological Treatment Options in Pediatric Glioblastoma—A Systematic Review

SIMPLE SUMMARY: Childhood glioblastoma is an aggressive brain tumor in children that has a very poor prognosis. Standard therapy includes surgery, irradiation and chemotherapy with temozolomide. So far, there is no effective drug treatment for pediatric glioblastoma patients. This systematic review aims to outline currently available data on novel pharmacological treatment options. None of the included phase II studies showed any benefit regarding overall survival or a prolongation of stable disease. New genomic technologies discovered the biologic heterogeneity of these tumors, demanding more individualized immunotherapeutic and targeted approaches. Autoimmune modulated therapies and further targeting of tumor-specific receptors provide promising preclinical results. Clinical trials aligned to the tumor characteristics are needed to establish effective new therapeutic approaches. ABSTRACT: Background: Pediatric glioblastoma (GBM) is an aggressive central nervous system tumor in children that has dismal prognosis. Standard of care is surgery with subsequent irradiation and temozolomide. We aimed to outline currently available data on novel pharmacological treatments for pediatric GBM. Methods: We conducted a systematic literature search in PubMed and Embase, including reports published in English from 2010 to 2021. We included randomized trials, cohort studies and case series. Phase I trials were not analyzed. We followed PRISMA guidelines, assessed the quality of the eligible reports using the Newcastle-Ottawa scale (NOS) and the RoB-2 tool and registered the protocol on PROSPERO. Results: We included 6 out of 1122 screened reports. All six selected reports were prospective, multicenter phase II trials (five single-arm and one randomized controlled trial). None of the investigated novel treatment modalities showed any benefit regarding overall or progression free survival. Conclusions: To date, the role of pharmacological approaches regarding pediatric GBM remains unclear, since no novel treatment approach could provide a significant impact on overall or progression free survival. Further research should aim to combine different treatment strategies in large international multicenter trials with central comprehensive diagnostics regarding subgrouping. These novel treatment approaches should include targeted and immunotherapeutic treatments, potentially leading to a more successful outcome.