Brigatinib: New-generation ALK inhibitor for nonsmall cell lung cancer

Curr Probl Cancer. 2019 Dec;43(6):100477. doi: 10.1016/j.currproblcancer.2019.03.005. Epub 2019 May 6.

Abstract

Lung cancer, specifically nonsmall cell lung cancer (NSCLC) is the leading cause of death around the world. First-line therapies for metastatic NSCLC such as crizotinib, a tyrosine kinase inhibitor (TKI), have developed resistance due to a rearrangement of the anaplastic lymphoma kinase (ALK) gene. Brigatinib, approved in May 2016, is an ALK inhibitor specifically indicated for ALK-positive metastatic NSCLC in patients who have progressed on or resistant to crizotinib therapy. In several clinical trials, brigatinib has exhibited significant improvement in progression-free survival in patients that have experienced resistance to crizotinib therapy. The optimal dose of brigatinib was found to be 180 mg once daily and demonstrated greater efficacy as compared to its 90 mg once daily dose. Brigatinib was also found to be well tolerated. Although more studies are needed, the current data from these studies indicate brigatinib may be the most favorable therapeutic approach to treat NSCLC ALK-positive patients.

Keywords: ALK; Brigatinib; Crizotinib-resistance; NSCLC; TKI.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / antagonists & inhibitors*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Organophosphorus Compounds / therapeutic use*
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*

Substances

  • Organophosphorus Compounds
  • Protein Kinase Inhibitors
  • Pyrimidines
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • brigatinib