Annotation Detail

Information
Associated Genes
BRAF
Associated Variants
BRAF V600
BRAF V600
Associated Disease
skin melanoma
Source Database
CIViC Evidence
Description
The Combi-v (NCT01597908) open-label, randomized phase 3 trial had 704 patients with metastatic melanoma with a BRAF V600 mutation. Patients were randomized to receive either a combination of dabrafenib and trametinib or vemurafenib orally as first-line therapy. At preplanned interim analysis the overall survival rate at 12 months was 72% (95% confidence interval [CI], 67 to 77) in the combination-therapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combination-therapy group, 0.69; 95% CI, 0.53 to 0.89; P=0.005). Median progression-free survival was 11.4 months in the combination-therapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0.69; P<0.001). Cutaneous squamous-cell carcinoma and keratoacanthoma occurred at 1% with combination-therapy and 18% in the vemurafenib group.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1411
Gene URL
https://civic.genome.wustl.edu/links/genes/5
Variant URL
https://civic.genome.wustl.edu/links/variants/17
Rating
5
Evidence Type
Predictive
Disease
Skin Melanoma
Evidence Direction
Supports
Drug
Trametinib,Dabrafenib
Evidence Level
A
Clinical Significance
Sensitivity/Response
Pubmed
25399551
Drugs
Drug NameSensitivitySupported
DabrafenibSensitivitytrue
TrametinibSensitivitytrue