Afatinib: first global approval

Drugs. 2013 Sep;73(13):1503-15. doi: 10.1007/s40265-013-0111-6.


Afatinib, an irreversible inhibitor of the ErbB family of tyrosine kinases, is under development with Boehringer Ingelheim for the once-daily, oral treatment of cancer. Afatinib downregulates ErbB signalling by covalently binding to epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER) 2 and HER4, irreversibly inhibiting tyrosine kinase autophosphorylation. It also inhibits transphosphorylation of HER3. Oral afatinib (Gilotrif™) has been approved in the US for the first-line treatment of patients with metastatic non-small-cell lung cancer (NSCLC) who have tumours with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by a US FDA-approved test. Afatinib has also been approved in Taiwan for the first-line treatment of patients with EGFR mutation-positive NSCLC. In addition, the European Medicines Agency's Committee for Medicinal Products for Human Use has recommended the approval of afatinib (Giotrif®) for the treatment of patients with locally advanced or metastatic NSCLC with activating EGFR mutations who are EGFR tyrosine kinase inhibitor naïve. Afatinib is also under regulatory review in Canada, Japan and other Asian countries. This article summarizes the milestones in the development of afatinib, leading to this first approval in patients with metastatic NSCLC.

Publication types

  • Review

MeSH terms

  • Afatinib
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemoradiotherapy* / adverse effects
  • Drug Approval
  • European Union
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Molecular Targeted Therapy* / adverse effects
  • Mutation
  • Neoplasm Grading
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics
  • Quinazolines / therapeutic use*
  • Radiation-Sensitizing Agents / adverse effects
  • Radiation-Sensitizing Agents / pharmacokinetics
  • Radiation-Sensitizing Agents / therapeutic use*
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Taiwan
  • United States
  • United States Food and Drug Administration


  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Quinazolines
  • Radiation-Sensitizing Agents
  • Afatinib
  • ERBB2 protein, human
  • Receptor, ErbB-2