Annotation Detail

Information
Associated Genes
EGFR
Associated Variants
EGFR MUTATION
EGFR MUTATION
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
In the ARCHER 1050 Phase 3 Trial (NCT01774721), 452 patients with newly diagnosed stage IIIB/IV or recurrent NSCLC exon 19 deletion or the Leu858Arg mutation, (with or without the T790M) were treated with second generation tyrosine kinase inhibitor (TKI) dacomitinib (227 patients) or first generation TKI gefitinib (225 patients). Primary endpoint was progression free survival (PFS), and median PFS according to masked independent review was 14.7 months (95% CI 11.1–16.6) with dacomitinib group 9.2 months (9.1–11.0) with gefitinib (HR 0·59, 95% CI 0·47–0·74; p<0·0001). Benefit of dacomitinib over gefitinib was lower in non-Asian patient subgroup (n=106) than in Asian group (n=346) although authors note smaller sample size may explain this. Authors state that PFS was significantly improved with first line dacomitinib treatment, and that dacomitinib should be considered for EGFR mutant NSCLC treatment.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7363
Gene URL
https://civic.genome.wustl.edu/links/genes/19
Variant URL
https://civic.genome.wustl.edu/links/variants/442
Rating
4
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Dacomitinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
28958502
Drugs
Drug NameSensitivitySupported
DacomitinibSensitivitytrue