Brigatinib in the first-line treatment of ALK+ metastatic NSCLC: safety and efficacy

Expert Rev Anticancer Ther. 2021 Aug;21(8):809-817. doi: 10.1080/14737140.2021.1923485. Epub 2021 May 13.

Abstract

Introduction: Among the oncogene-addicted non-small cell lung cancer patients, those bearing ALK rearrangement can be currently treated with next-generation ALK inhibitors. Brigatinib was first used to treat Crizotinib-resistant patients because it can target resistance mutations in ALK fusion protein. Recently, Brigatinib was also studied as upfront treatment of newly diagnosed ALK-positive patients.Areas covered: We outline the drug profile of Brigatinib as first-line treatment and compare it with other ALK inhibitors available. The context of ALK-rearranged non-small cell lung cancer and pharmacological aspects of Brigatinib are reviewed before the analysis of the results from the study ALTA-1 L in terms of efficacy and safety.Expert opinion: The superior efficacy of Brigatinib over Crizotinib as first-line treatment is undoubted. Consequently, Brigatinib is a new option in untreated ALK+ metastatic NSCLC patients, among the other drugs available for this indication, such as Ceritinib and Alectinib. Each of these ALK inhibitors has a specific tolerability profile, so that the choice may be also guided by patient preference according to potential side effects. In the future other factors could impact treatment choice, for instance the kind of resistance ALK mutations develop under treatment could influence the sequence of ALK inhibitors.

Keywords: ALK inhibitor; ALTA-1L; Non-small cell lung cancer; brigatinib; oncogene-addicted.

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Organophosphorus Compounds / adverse effects
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines

Substances

  • Organophosphorus Compounds
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Anaplastic Lymphoma Kinase
  • brigatinib