Lung cancer<unk>  in unresectable non-small cell lung cancer when added to chemotherapy improves overall survival by 19%, and improved progression-free survival (PFS) by 29%, when compared to chemotherapy alone. The U.S. Food and Drug Administration (FDA) approved<unk>  for the treatment of locally advanced or metastatic non-small cell lung cancer that has failed at least one prior chemotherapy regimen. In lung cancer,<unk>  has been shown to be effective in patients with or without EGFR mutations, but appears to be more effective in patients with EGFR mutations. Overall survival, progression-free survival and one-year survival are similar to standard second-line therapy (docetaxel or pemetrexed). Overall response rate is about 50% better than standard second-line chemotherapy. Patients who are non-smokers, and light former smokers, with adenocarcinoma or subtypes like BAC are more likely to have EGFR mutations, but mutations can occur in all types of patients. A test for the EGFR mutation has been developed by Genzyme. Pancreatic cancer In November 2005, the FDA approved<unk>  in combination with gemcitabine for treatment of locally advanced, unresectable, or metastatic pancreatic cancer. Resistance to treatment<unk>  bound to ErbB1 at 2.6A resolution; surface colour indicates hydrophobicity. As with other ATP competitive small molecule tyrosine kinase inhibitors, such as imatinib in CML, patients rapidly develop resistance. In the case of<unk>  this typically occurs 8–12 months from the start of treatment. Over 50% of resistance is caused by a mutation in the ATP binding pocket of the EGFR kinase domain involving substitution of a small polar threonine residue with a large nonpolar methionine residue (T790M). Approximately 20% of drug resistance is caused by amplification of the hepatocyte growth factor receptor, which drives ERBB3 dependent activation of PI3K.
Erlotinib
Nilotinib
Afatinib
Axitinib
Sunitinib
Icotinib
Crizotinib
Tepotinib