Predicting clinical benefit in non-small-cell lung cancer patients treated with epidermal growth factor tyrosine kinase inhibitors.
Erlotinib and gefitinib are small-molecule inhibitors of the epidermal growth factor tyrosine kinase. Erlotinib is approved for the treatment of locally advanced or metastatic non-small-cell lung cancer after failure of at least one prior chemotherapy regimen. Although it is active in unselected patients, clinical characteristics and tumor molecular markers associated with enhanced benefit have been identified. Notably, never-smoker status or a positive EGFR FISH test has been consistently predictive of greater erlotinib benefit. Other markers, such as EGFR mutations and EGFR protein expression, as determined by immunohistochemistry, and KRAS mutation status have not proven to be consistently associated with differential benefit.
Amler
L C
LC
Development Sciences, Genentech, Inc., South San Francisco, California 94080, USA.
Goddard
A D
AD
Hillan
K J
KJ
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D018628:Gene Dosage; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib