An updated review on systemic therapy for brain metastases in non-small cell lung cancer

Brain metastases (BrM) are a frequent and devastating complication of non-small cell lung cancer (NSCLC), affecting up to 40% of patients during their disease course. Historically, treatment relied primarily on surgery and radiation, as systemic therapies were thought to have limited activity in the central nervous system (CNS). However, over the past two decades, the development of more targeted therapies has transformed the treatment landscape. Many of these newer agents have improved CNS penetration, which may offer patients the possibility of deferring or reducing the need for local therapies and their associated toxicities. Despite these advances, many challenges remain. There is still a lack of consistent inclusion of BrM patients in clinical trials, and when they are included, there are inconsistencies in measuring radiographic responses as well as in standardized CNS-specific endpoints, making it difficult to compare outcomes across therapies. As treatment options expand, the integration of systemic therapies with surgery and radiation requires nuanced, multidisciplinary decision-making tailored to individual patients. In this review, we aim to summarize the current treatment landscape of pertinent therapies for BrM in NSCLC patients while highlighting the need for broadening inclusion of these patients and creating well-designed prospective studies that intentionally include patients with active and untreated BrM alongside rigorously assess intracranial outcomes. Such efforts will be critical to developing treatment plans in order to ultimately improve survival and quality of life for NSCLC patients with BrM.