Annotation Detail

Information
Associated Genes
BRAF
Associated Variants
BRAF p.Val640Glu (p.V640E) ( ENST00000288602.11, ENST00000496384.7, ENST00000644969.2, ENST00000646891.2 )
BRAF p.Val640Glu (p.V640E) ( ENST00000288602.11, ENST00000496384.7, ENST00000644969.2, ENST00000646891.2 )
Associated Disease
melanoma
Source Database
CIViC Evidence
Description
In this Phase III trial (NCT01584648 COMBI-d), previously untreated patients with unresectable stage IIIC or IV melanoma with BRAF V600E (359 patients) or V600K (61 patients) received dabrafenib and trametinib or dabrafenib alone with primary endpoint of progression free survival and secondary endpoints including disease response. The hazard ratio for progression or death in the V600E group was 0.81 for dabrafenib-trametinib vs dabrafenib-alone. Of 179 V600E patients in the dabrafenib-trametinib group, 68% of patients had a response, which was 15 percentage points higher than in the dabrafenib-alone group (95% CI, 4 to 24; P=0.006).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/6938
Gene URL
https://civic.genome.wustl.edu/links/genes/5
Variant URL
https://civic.genome.wustl.edu/links/variants/12
Rating
5
Evidence Type
Predictive
Disease
Melanoma
Evidence Direction
Supports
Drug
Trametinib,Dabrafenib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
25265492
Drugs
Drug NameSensitivitySupported
DabrafenibSensitivitytrue
TrametinibSensitivitytrue