Rapid response of brain metastases to alectinib in a patient with non-small-cell lung cancer resistant to crizotinib

Med Oncol. 2015 Feb;32(2):477. doi: 10.1007/s12032-014-0477-7. Epub 2015 Jan 3.

Abstract

Crizotinib is a potent and specific small-molecule inhibitor of both anaplastic lymphoma kinase (ALK) and c-MET tyrosine kinases, and patients with ALK rearrangement tumor benefit from crizotinib treatment; however, its penetration into calculated cerebrospinal fluid (CSF) is considered to be poor. Alectinib is a highly selective, next-generation ALK inhibitor, and both preclinical and clinical studies have indicated that alectinib is also effective in crizotinib-resistant tumors. A recent in vitro study demonstrated significant antitumor activity of alectinib for brain metastases using mouse models of ALK-positive non-small-cell lung cancer. In this paper, we report a first case alectinib was highly effective against brain metastases refractory to crizotinib. Further investigation of alectinib in this setting would be particularly valuable.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary
  • Carbazoles / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Crizotinib
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics
  • Piperidines / therapeutic use*
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use

Substances

  • Antineoplastic Agents
  • Carbazoles
  • EML4-ALK fusion protein, human
  • Oncogene Proteins, Fusion
  • Piperidines
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • alectinib