Biomarkers for prediction of sensitivity to EGFR inhibitors in non-small cell lung cancer.
OBJECTIVE
Epidermal growth factor receptor (EGFR) Inhibitors have shown promising results in patients with advanced non-small cell lung cancers (NSCLC) who previously have failed on chemotherapy. Objective response is achieved in 10 to 28% of the patients, and about 30% will achieve stable disease. A major problem is how to select the patients, who will benefit from treatment, and who will not.


RESULTS
The predictive role of EGFR protein expression assessed by IHC is still debated. Specific EGFR gene mutations have been identified associated with response to gefitinib (Iressa(R)), but seem not to be associated with stable disease. No studies have yet demonstrated any association between EGFR gene mutations and survival. In this review we describe other marker studies, which are associated with sensitivity to EGFR inhibitors. Increased EGFR gene copy number based on FISH analysis is demonstrated to be a good predictive marker for response, stable disease, time to progression, and survival.


CONCLUSIONS
EGFR/FISH seems today to be the best predictive marker for clinical benefit from EGFR inhibitors in NSCLC. Prospective large scale clinical studies must identify the most optimal paradigm for selection of patients.
Hirsch
Fred R
FR
University of Colorado Cancer Center, Department of Medicine/Medical Oncology and Pathology, Aurora, Colorado 80010, USA. Fred.Hirsch@UCHSC.edu
Witta
Samir
S
D000970:Antineoplastic Agents / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors