Annotation Detail

Information
Associated Genes
EGFR
Associated Variants
EGFR p.Thr790Met (p.T790M) ( ENST00000275493.7, ENST00000450046.2, ENST00000455089.5 )
EGFR p.Thr790Met (p.T790M) ( ENST00000275493.7, ENST00000450046.2, ENST00000455089.5 )
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
In an in vitro study using NCI-H1666 cells (wildtype EGFR) and NCI-H1975 cells (EGFR-L858R/T790M), inhibition of cell growth was used as an assay to determine sensitivity to tyrosine kinase inhibitor (TKI) drugs. Cells with an EGFR L858R/T790M mutation demonstrated an improved response to afatinib (IC50: 99nM vs. >4000nM) compared to the same cells treated with erlotinib. In an in vivo mouse xenograft study, the growth of cells with an EGFR-L858R/T790M mutation were more sensitive to treatment of afatinib (concentration: 15-20mg/kg) (median tumor volume = 75-150mm^3 vs. 1000mm^3), compared to reversible TKI lapatinib-treated xenografts. However, no complete responses were observed with afatinib alone.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/2163
Gene URL
https://civic.genome.wustl.edu/links/genes/19
Variant URL
https://civic.genome.wustl.edu/links/variants/34
Rating
2
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Afatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
18408761
Drugs
Drug NameSensitivitySupported
AfatinibSensitivitytrue