Pharmacotherapeutic advances with anaplastic lymphoma kinase inhibitors for the treatment of non-small cell lung cancer

Expert Opin Pharmacother. 2020 Jun;21(8):931-940. doi: 10.1080/14656566.2020.1738387. Epub 2020 Mar 12.

Abstract

Introduction: Anaplastic lymphoma kinase (ALK) inhibitors are potent oral anti-cancer agents acting as tyrosine kinase inhibitors (TKIs), which are approved for the treatment of ALK+ non-small cell lung cancer (NSCLC). Over the last years, several new molecules have been developed and are currently under clinical investigation.

Areas covered: In this paper, the authors review the most relevant clinical findings of ALK inhibitors in the treatment of ALK+ NSCLC. The authors discuss differences in the efficacy and treatment-related adverse events (AEs) incidence of distinct ALK inhibitors, molecular mechanisms of acquired resistance, and ongoing clinical studies assessing the use of ALK inhibitors in innovative settings and novel combinations.

Expert commentary: ALK inhibitors have dramatically improved the prognosis of patients with ALK+ NSCLC and revolutionized therapy options. Nowadays, several molecules are approved for the treatment of ALK+ NSCLC, either in first or further lines of systemic treatment. Several clinical trials are currently ongoing in order to define a potential role of ALK inhibitors in combination with novel anti-cancer agents, as well as monotherapy in neo- and adjuvant settings.

Keywords: Non-small cell lung cancer; alectinib; brigatinib; ceritinib; crizotinib; ensartinib; lorlatinib.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / antagonists & inhibitors*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Clinical Trials as Topic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Anaplastic Lymphoma Kinase