Role of Precision Medicine in Patients with CNS Metastasis

Brain metastases are associated with poor prognosis, due to significant neurologic morbidity and current lack of a durable central nervous system (CNS)-directed therapy. Consequently, brain metastases are a critical unmet need, as the incidence is rising as treatment for systemic cancer improves. One recent breakthrough for brain metastases has been the recognition of spatial and temporal genomic heterogeneity across different metastatic sites. Recent genomic analyses have demonstrated the presence of actionable driver mutations within brain metastases not present in the paired primary tumors. This genomic heterogeneity likely contributes to the clinically observed divergent response seen with intracranial and extracranial disease burden. Another promising development has been the advent of next-generation targeted agents and immunotherapies, which have demonstrated improved tolerability and promising response rates for CNS disease. In this review, we discuss and highlight current noninvasive efforts to obtain genomic information, known genomic drivers of disease, and opportunities for targeted therapies for brain metastases.