Brain metastases in non-small-cell lung cancer: are tyrosine kinase inhibitors and checkpoint inhibitors now viable options?

Curr Oncol. 2018 Jun;25(Suppl 1):S103-S114. doi: 10.3747/co.25.3733. Epub 2018 Jun 13.


Significant progress has been made in the treatment of stage iv non-small-cell lung cancer (nsclc); however, the prognosis of patients with brain metastases remains poor. Resection and radiation therapy remain standard options. This issue is an important one because 10% of patients with nsclc have brain metastases at diagnosis, and 25%-40% develop brain metastases during their disease. Standard chemotherapy does not cross the blood-brain barrier. However, there is new hope that tyrosine kinase inhibitors (tkis) used in patients with identified targetable mutations such as mutations of EGFR and rearrangements of ALK could have activity in the central nervous system (cns). Furthermore, immunotherapy is increasingly becoming a standard option for patients with nsclc, and interest about the intracranial activity of those agents is growing. This review presents current data about the cns activity of the available major tkis and immunotherapy agents.

Keywords: ALK; EGFR; Non-small-cell lung cancer; afatinib; alectinib; ceritinib; crizotinib; epidermal growth factor receptor; immunotherapy; nivolumab; nsclc; osimertinib; pembrolizumab; tkis; tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Drug Resistance, Neoplasm / drug effects
  • Genes, cdc / drug effects
  • Genes, cdc / immunology
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology*
  • Neoplasm Staging
  • Prognosis
  • Protein Kinase Inhibitors / classification
  • Protein Kinase Inhibitors / therapeutic use*


  • Protein Kinase Inhibitors