Systemic Therapy of Lung Cancer CNS Metastases Using Molecularly Targeted Agents and Immune Checkpoint Inhibitors

Central nervous system (CNS) metastases most commonly arise from lung cancer, with the majority of patients affected during their disease course. The prognosis for patients with untreated brain metastases is poor, with surgical resection and/or radiotherapy as classic therapeutic options. However, the value of systemic therapy in the management of CNS metastases from lung cancer is growing. Novel targeted agents for the treatment of non-small cell lung cancer (NSCLC) have demonstrated activity in treating patients with CNS involvement, and are potential alternatives to radiation and surgery. These agents include anaplastic lymphoma kinase (ALK) inhibitors such as alectinib, crizotinib, ceritinib, lorlatinib, and others; epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, including the recently developed third-generation inhibitor osimertinib, and even immune checkpoint inhibitors such as nivolumab, pembrolizumab, and atezolizumab. This review summarizes current activity of systemic agents in the management of CNS metastases from NSCLC, as well as potential mechanisms of action of these small and large molecules.