The impact of systemic precision medicine and immunotherapy treatments on brain metastases

Metastases from melanoma, lung and breast cancer are among the most common causes of intracranial malignancy. Standard of care for brain metastases include a combination of surgical resection, stereotactic radiosurgery, and whole-brain radiation. However, evidence continues to accumulate regarding the efficacy of molecularly-targeted systemic treatments and immunotherapy. For non-small cell lung cancer (NSCLC), numerous clinical trials have demonstrated intracranial activity for inhibitors of EGFR and ALK. Patients with melanoma brain metastases may benefit from systemic therapy using BRAF-inhibitors with and without trametinib. Several targeted options are available for breast cancer brain metastases that overexpress HER2, although agents with intracranial activity are still needed for other molecular subtypes. Immune checkpoint inhibitors including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies are yielding impressive responses in intracranial manifestations of metastatic melanoma and NSCLC. Given the promising early results with these emerging therapies, management of eligible patients will require increased multidisciplinary discussion incorporating novel systemic treatment approaches prior or in addition to local therapy.