Epidermal growth factor receptor genomic variation in NSCLC patients receiving tyrosine kinase inhibitor therapy: a systematic review and meta-analysis.
BACKGROUND
The objective of this analysis was to examine the relationship between genomic variation and health outcomes in studies performed in non-small cell lung cancer (NSCLC) patients treated with single agent epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) using a systematic review with statistical pooling of data.


METHODS
We performed a systematic search of the literature using the MEDLINE, BIOSIS, and EMABASE databases from July 1997 to July 2007. Eligible studies were evaluated for quality and clinical, methodological, and statistical heterogeneity. Abstracted data judged to be sufficiently homogenous were pooled using a fixed effect model.


RESULTS
We found a statistically significant higher probability of tumor response (according to the RECIST criteria) for patients with EGFR mutations versus wild type (5.92, 95% CI 4.91-7.13) and patients with high- versus low EGFR protein expression (2.71, 95% CI 1.72-4.29). EGFR mutation and high EGFR protein expression were associated with significantly improved survival over the wild type and low protein expression groups (0.36, 95% CI 0.29-0.46 and 0.59, 95% CI 0.44-0.81), respectively. Last, there was a significant difference in EGFR-TKI treatment effect in the high EGFR gene copy number and high EGFR protein expression groups (0.72, 95% CI 0.57-0.92 and 0.53, 95% CI 0.35-0.80).


CONCLUSIONS
In conclusion, EGFR mutation and protein expression status may provide useful clinical information in terms of the likelihood of tumor response and disease prognosis. EGFR gene copy number and to a lesser extent, EGFR protein expression status, appear to be promising biomarkers for predicting a survival benefit with EGFR-TKI therapy in second line NSCLC, but further evidence is needed.
Carlson
Josh John
JJ
Pharmaceutical Outcomes Research and Policy Program, School of Pharmacy, University of Washington, Seattle, WA 98195, USA. carlsojj@u.washington.edu
Garrison
Louis P
LP
Ramsey
Scott D
SD
Veenstra
David L
DL
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D003627:Data Interpretation, Statistical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic / Q000592:standards
D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors