Pharmacotherapeutic options for treating brain metastases in non-small cell lung cancer

Expert Opin Pharmacother. 2015;16(17):2601-13. doi: 10.1517/14656566.2015.1094056. Epub 2015 Oct 6.

Abstract

Introduction: Central nervous system (CNS) metastases represent an important cause of morbidity and mortality in non-small cell lung cancer (NSCLC) patients. Local approaches of neurosurgery (usually for single brain lesions), whole brain radiotherapy, and stereotactic radiosurgery are often withheld for the treatment of NSCLC-derived brain metastases (BMs). However, systemic treatment is consistently emerging as an option for patients with asymptomatic BMs, which could allow for delaying cranial radiotherapy at symptomatic/radiological progression.

Areas covered: Chemotherapy, monoclonal antibodies, tyrosine-kinase inhibitors (TKIs) for molecularly selected NSCLCs, such as epidermal growth factor receptor (EGFR)-mutant and anaplastic lymphoma kinase (ALK)-rearranged diseases, and immune checkpoint inhibitors are all systemic treatments that have shown activity against NSCLC-derived CNS metastases. Among these, EGFR- and ALK-TKIs will be discussed more in detail owing to their superior efficacy in this context.

Expert opinion: Up-front systemic treatment should be considered for patients with asymptomatic, multiple BMs, as recently acknowledged by the European Society of Medical Oncology guidelines. Nevertheless, it must be emphasized that the best treatment strategy for NSCLC-derived BMs has to be defined within a multidisciplinary team.

Keywords: bevacizumab; brain metastases; central nervous system metastases; cerebro-spinal fluid; chemotherapy; immune checkpoint inhibitors; non-small cell lung cancer; tyrosine-kinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / immunology
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Combined Modality Therapy
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / genetics
  • Treatment Failure

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases