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
Randomized, international, open-label, phase 3 trial (NCT02151981) in 419 patients with T790M-positive advanced NSCLC and disease progression after first-line EGFR-TKI therapy. Patients were randomized, in a 2:1 ratio, to oral osimertinib or chemotherapy (pemetrexed plus either carboplatin or cisplatin every 3 weeks for up to six cycles, maintenance pemetrexed was allowed). Primary end point was PFS, which was significantly longer with osimertinib than with chemotherapy (10.1 months vs. 4.4 months; HR 0.30; 95% CI: 0.23 to 0.41; P<0.001). Objective response rate was significantly better with osimertinib (71%; 95% CI, 65 to 76) than with chemotherapy (31%; 95% CI, 24 to 40) (odds ratio for objective response, 5.39; 95% CI, 3.47 to 8.48; P<0.001).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1867
Gene URL
https://civic.genome.wustl.edu/links/genes/19
Variant URL
https://civic.genome.wustl.edu/links/variants/34
Rating
5
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Osimertinib
Evidence Level
A
Clinical Significance
Sensitivity/Response
Pubmed
27959700
Drugs
Drug NameSensitivitySupported
OsimertinibSensitivitytrue