An update on molecularly targeted therapies in second- and third-line treatment in non-small cell lung cancer: focus on EGFR inhibitors and anti-angiogenic agents

Clin Transl Oncol. 2013 May;15(5):343-57. doi: 10.1007/s12094-012-0964-2. Epub 2013 Jan 29.


Docetaxel, pemetrexed and epidermal growth factor receptor tyrosine kinase inhibitors (gefitinib and erlotinib) are recommended second-line therapy for advanced non-small cell lung cancer (NSCLC) patients with disease progression. Although erlotinib is the only recommended third-line therapy, several drugs are being used in the clinic. Recent studies have focused on combining targeted agents with approved therapies, including broad-spectrum multikinase inhibitors targeting multiple ErbB Family receptors and multitargeted anti-angiogenic agents targeting the vascular endothelial growth factor receptor, platelet-derived growth factor receptor and fibroblast growth factor receptor pathways. Here, we review targeted therapies that are being evaluated in second- and third-line settings in NSCLC, including the ErbB Family Blocker afatinib (BIBW 2992), multityrosine kinase inhibitors (pelitinib [EKB-56]), neratinib [HKI-272], canertinib [CI-1033], lapatinib [GW-572016], dacomitinib [PF-299804]) and multitargeted anti-angiogenic agents (vandetanib [ZD6474], sunitinib [SU11248], sorafenib [BAY43-9006], nintedanib [BIBF1120], axitinib [AG-013736], cediranib [AZD2171], motesanib [AMG 706], linifanib [ABT869] and pazopanib [GW786034]).

Publication types

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

MeSH terms

  • Afatinib
  • Aminoquinolines / therapeutic use
  • Angiogenesis Inhibitors / therapeutic use*
  • Aniline Compounds / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Lapatinib
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / drug therapy*
  • Molecular Targeted Therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use
  • Quinolines / therapeutic use


  • Aminoquinolines
  • Angiogenesis Inhibitors
  • Aniline Compounds
  • Protein Kinase Inhibitors
  • Quinazolines
  • Quinolines
  • Lapatinib
  • Afatinib
  • ErbB Receptors
  • neratinib
  • EKB 569