Afatinib: Emerging next-generation tyrosine kinase inhibitor for NSCLC

Valerie Nelson, Jacqueline Ziehr, Mark Agulnik, Melissa Johnson*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

70 Scopus citations

Abstract

The discovery of epidermal growth-factor receptor (EGFR)-activating mutations and the introduction of oral EGFR tyrosine kinase inhibitors (EGFR-TKIs) have expanded the treatment options for patients with non-small cell lung cancer. The first two reversible EGFR-TKIs, erlotinib and gefitinib, are approved for use in the first-line setting in patients with known EGFR-activating mutations and in the second- and third-line settings for all NSCLC patients. These first-generation EGFR-TKIs improve progression-free survival when compared to chemotherapy in patients with EGFR-activating mutations in the first-line setting. However, nearly all patients develop resistance to EGFR-directed agents. There is a need for further therapy options for patients with disease progression after treatment with reversible EGFR-TKIs. Afatinib is an irreversible ErbB family blocker that inhibits EGFR, HER2, and HER4. In vitro and in vivo, afatinib have shown increased inhibition of the common EGFR-activating mutations as well as the T790M resistance mutation when compared to erlotinib and gefitinib. Clinically, afatinib has been evaluated in the LUX-Lung series of trials, with improvement in progression-free survival reported in patients with EGFR-activating mutations in both first- and second-/third-line settings when compared to chemotherapy. Further investigation is needed to determine the precise role that afatinib will play in the treatment of patients with non-small cell lung cancer and EGFR-activating mutations.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalOncoTargets and Therapy
Volume6
DOIs
StatePublished - 2013

Keywords

  • Afatinib
  • EGFR
  • EGPR-TKIs
  • Irreversible EGFR inhibitor
  • LUX lung
  • Resistance mutation
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

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