Afatinib: An overview of its clinical development in non-small-cell lung cancer and other tumors

Crit Rev Oncol Hematol. 2016 Jan:97:143-51. doi: 10.1016/j.critrevonc.2015.08.016. Epub 2015 Aug 12.

Abstract

Afatinib is an oral, irreversible, tyrosine kinase inhibitor (TKI) of EGFR, HER2 and HER4. According to phase I studies, the recommended dose of afatinib was 50mg daily. Rash, acne, diarrhea and stomatitis were the most common adverse events. Afatinib failed to demonstrate an improvement in overall survival in unselected heavily pretreated NSCLC patients (Lux-Lung-1). On the contrary, the Lux-Lung-3 and -6 trials met the primary end point, demonstrating a significant increase in terms of PFS with afatinib compared with chemotherapy in the first line treatment of EGFR mutant patients. Moreover, in both studies, afatinib improved overall survival in patients with exon 19 EGFR deletion (31.7 vs 20.7 months; HR: 0.59, p=0.0001). The results of ongoing randomized trials should further clarify the efficacy of afatinib compared with first-generation TKIs in advanced NSCLC, its activity in the adjuvant and neoadjuvant settings, as well as its efficacy in other tumors.

Keywords: Afatinib; Clinical trials; EGFR; Head-neck; NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Afatinib
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • ErbB Receptors / antagonists & inhibitors
  • Humans
  • Lung Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / therapeutic use*
  • Randomized Controlled Trials as Topic

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Afatinib
  • ErbB Receptors