Irreversible tyrosine kinase inhibition of epidermal growth factor receptor with afatinib in EGFR activating mutation-positive advanced non-small-cell lung cancer

Curr Oncol. 2018 Jun;25(Suppl 1):S9-S17. doi: 10.3747/co.25.3732. Epub 2018 Jun 13.

Abstract

Despite recent advances in the systemic therapy of non-small-cell lung cancer (nsclc), the prognosis for stage iv disease remains poor. The discovery of targetable mutations has led to new treatment options. The most common mutations, the EGFR activating mutations, are present in about 50% of Asian patients and up to 15% of white patients. First-generation reversible epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) have led to improved survival in patients positive for EGFR activating mutations, but resistance eventually leads to disease progression. The irreversible egfr tki afatinib was developed to counter such resistance. The clinical efficacy of afatinib has been shown in first-line studies comparing it with both cytotoxic chemotherapy and first-generation egfr tkis. Afatinib has also shown continued benefit beyond progression while a patient is taking an egfr inhibitor. Furthermore, its toxicity profile is both predictable and manageable. The results of the principal clinical trials assessing afatinib are reviewed here.

Keywords: Non-small-cell lung cancer; afatinib; egfr; epidermal growth factor receptor; nsclc; tkis; tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Afatinib / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Progression
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Gain of Function Mutation / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • Afatinib
  • EGFR protein, human
  • ErbB Receptors