Safety of alectinib for the treatment of metastatic ALK-rearranged non-small cell lung cancer

Expert Opin Drug Saf. 2017 Apr;16(4):509-514. doi: 10.1080/14740338.2017.1299706. Epub 2017 Mar 3.

Abstract

Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) may derive significant clinical benefit from targeted therapies against this driver mutation, but progression is virtually inevitable. Alectinib is a next-generation ALK inhibitor that provides a novel treatment option for this group of patients. Areas covered: In this review, we summarize the overall safety and tolerability of alectinib. Specifically, we cover cardiovascular, gastrointestinal, hepatic, musculoskeletal, and respiratory adverse events. The safety profile of alectinib is also described in special populations and in comparison with other ALK inhibitors. Expert opinion: Alectinib is a well-tolerated tyrosine kinase inhibitor and should be considered for patients with ALK-rearranged NSCLC. The question then arises as to how to choose a next-generation ALK inhibitor in the second-line setting. Understanding acquired resistant mechanisms has become essential. Whether or not to use alectinib in the first-line setting is extremely controversial, but we anticipate its approval for this indication and availability in more countries in the near future.

Keywords: ALK inhibitor; Alectinib; non-small-cell lung cancer; safety; tolerability.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carbazoles / adverse effects
  • Carbazoles / pharmacology
  • Carbazoles / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Mutation
  • Piperidines / adverse effects
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / genetics

Substances

  • Antineoplastic Agents
  • Carbazoles
  • Piperidines
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • alectinib