Abstract
Simple SummaryPrimary brain tumors are rare neoplasms with limited effective systemic treatment options. Recent advances in new molecular techniques have brought about novel information about molecular markers and potential targetable molecular alterations in brain tumors. Targeted therapeutic approaches are already established in several extracranial malignancies and its application is increasingly used and studied in the management of primary brain tumors. The aim of this article is to summarize the latest progress in precision medicine approaches in primary brain tumors.Primary central nervous system (CNS) tumors represent a heterogenous group of tumors. The 2021 fifth edition of the WHO Classification of Tumors of the CNS emphasizes the advanced role of molecular diagnostics with routine implementation of molecular biomarkers in addition to histologic features in the classification of CNS tumors. Thus, novel diagnostic methods such as DNA methylome profiling are increasingly used to provide a more precise diagnostic work-up of CNS tumors. In addition to these diagnostic precision medicine advantages, molecular alterations are also addressed therapeutically with targeted therapies. Like in other tumor entities, precision medicine has therefore also arrived in the treatment of CNS malignancies as the application of targeted therapies has shown promising response rates. Nevertheless, large prospective studies are currently missing as most targeted therapies were evaluated in single arm, basket, or platform trials. In this review, we focus on the current evidence of precision medicine in the treatment of primary CNS tumors in adults. We outline the pathogenic background and prevalence of the most frequent targetable genetic alterations and summarize the existing evidence of precision medicine approaches for the treatment of primary CNS tumors.
Highlights
We summarize the current evidence on targeted therapies with focus on v-rapidly accelerating fibrosarcoma (RAF) Murine Sarcoma Viral Oncogene Homolog B1 (BRAF), isocitrate dehydrogenase
The glioma subgroup in this study showed In IDH1 mutated glioma, a multicenter open-label phase I dose escalation study of an overall response rate of 25% [82]
A pooled analysis of these studies which enrolled a total of 159 patients with advanced or metastatic non-central nervous system (CNS) primary neurotrophic tyrosine receptor kinase (NTRK)-fusion positive solid tumors demonstrated response rates after treatment with larotrectinib of >75%
Summary
All of these studies did not meet their primary endpoint, showing that PD-1 immune checkpoint inhibition treatment did not improve overall survival (OS) in glioblastoma patients, neither at initial diagnosis nor at recurrence [3,4,5] Pembrolizumab represents another PD-1 inhibitor which has been investigated in phase I/II trials in primary brain tumors. EGFR inhibition: Many approaches to target EGFR have been developed, including therapy with small molecule TKIs (for example, gefitinib and lapatinib), monoclonal antibodies (cetuximab, nimotuzumab), antibody drug conjugates (depatuxizumab mafodotin) or vaccination with rindopepimut None of these agents demonstrated outcome benefit in primary brain tumors [14,27,28,29,30,31]. 1 (IDH) and neurotrophic tyrosine receptor kinase (NTRK) fusion in a precision medicine approach for adult primary brain tumors
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