Annotation Detail

Information
Associated Genes
BRAF
Associated Variants
BRAF V600
BRAF V600
Associated Disease
melanoma
Source Database
CIViC Evidence
Description
Patients who had histologically confirmed, unresectable stage IIIC or IV cutaneous melanoma with a V600E or V600K BRAF mutation were eligible for the study. 322 eligible patients (281 with the V600E mutation, 40 with the V600K mutation, and 1 with both mutations) in a 2:1 ratio to receive oral trametinib (2 mg once daily) or intravenous chemotherapy consisting of either dacarbazine (1000 mg per square meter of body-surface area) or paclitaxel (175 mg per square meter), at the discretion of the investigator, every 3 weeks. The primary end point was progression-free survival; secondary end points included overall survival, overall response rate, duration of response, and safety. Treatment continued until disease progression, death, or withdrawal from the study. In the intention-to-treat population, the median duration of progression-free survival was 4.8 months in the trametinib group as compared with 1.5 months in the chemotherapy group (hazard ratio for progression, 0.45; 95% confidence interval [CI], 0.33 to 0.63; P<0.001). The 6-month overall survival rate in the intention-to-treat population was 81% in the trametinib group and 67% in the chemotherapy group.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1750
Gene URL
https://civic.genome.wustl.edu/links/genes/5
Variant URL
https://civic.genome.wustl.edu/links/variants/17
Rating
3
Evidence Type
Predictive
Disease
Melanoma
Evidence Direction
Supports
Drug
Trametinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
22663011
Drugs
Drug NameSensitivitySupported
TrametinibSensitivitytrue