Lung Cancer with Brain Metastasis-Treatment Strategies and Molecular Characteristics

Lung cancer is a leading cause of brain metastases (BMs), with 10-20% of patients with non-small cell lung cancer (NSCLC) presenting with BMs at diagnosis and 25-50% developing them over the course of their disease. Historically, BMs have posed significant therapeutic challenges, partly due to the blood brain barrier (BBB), which restricts drug penetration to the central nervous system. Consequently, BMs were initially managed with local treatments, including surgical resection, stereotactic radiosurgery, and whole brain radiation therapy. In recent years, however, systemic treatments for BMs have advanced significantly, particularly with the development of molecularly-targeted therapies and immunotherapies. The discovery of driver mutations and the development of novel tyrosine kinase inhibitors (TKIs) have yielded encouraging intracranial responses in NSCLC patients with actionable genetic alterations (e.g., EGFR, ALK, ROS1). Genomic profiling has also suggested genetic heterogeneity between BMs and primary sites. Immunotherapies, alone or in combination with other treatments, have demonstrated promising results in NSCLC with BMs, although most clinical trials have included only selected patients with asymptomatic or previously treated BMs. In this review, we discuss the molecular and immune characteristics of NSCLC with BMs, analyze intracranial efficacy findings from clinical trials, and explore treatment strategies for lung cancer patients with BMs.