Precision medicine approaches to CNS metastatic disease

Brain metastases (BrM) and leptomeningeal metastases (LM) are increasingly common neurologic complications of cancer. The era of precision oncology has ushered in a deeper understanding of the molecular alterations that drive oncogenesis, subsequently informing and accelerating the drug development process. New systemic treatments, including oral tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) as well as antibody-drug conjugates (ADCs), have substantial intracranial efficacy with meaningful clinical benefit for BrM patients. Our understanding of LM continues to evolve with the development of improved detection methods and an increasing number of brain penetrant therapies. Targeted therapeutics continue to transform the existing treatment landscape and add both choice and complexity to the clinician's calculus when managing patients with BrM and/or LM. Multidisciplinary discussion should ultimately guide all treatment decisions and explore both the benefits and toxicities of various therapy options. Systemic targeted therapies should be considered for patients with asymptomatic or minimally symptomatic small BrM and/or LM. Future studies investigating treatment timing and effective combinatorial strategies are urgently needed.