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

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Abstract

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.

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  1. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 7W-389, 700 University Avenue, Toronto, ON, M5G 1Z5, Canada

    Grainne M. O’Kane & Natasha B. Leighl

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Grainne M. O’Kane is supported by the Division of Medical Oncology/Hematology, Princess Margaret Cancer Centre, and Natasha B. Leighl is supported by the Princess Margaret Cancer Foundation OSI Pharmaceuticals Foundation Chair in Cancer New Drug Development. No external funding support was provided for this review.

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Grainne M. O’Kane and Natasha B. Leighl declare that they have no conflicts of interest that might be relevant to the contents of this review.

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O’Kane, G.M., Leighl, N.B. Systemic Therapy of Lung Cancer CNS Metastases Using Molecularly Targeted Agents and Immune Checkpoint Inhibitors. CNS Drugs 32, 527–542 (2018). https://doi.org/10.1007/s40263-018-0526-4

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