Annotation Detail

Information
Associated Genes
BRAF
Associated Variants
BRAF p.Val640Lys (p.V640K) ( ENST00000288602.11, ENST00000496384.7, ENST00000644969.2, ENST00000646891.2 )
BRAF p.Val640Lys (p.V640K) ( ENST00000288602.11, ENST00000496384.7, ENST00000644969.2, ENST00000646891.2 )
Associated Disease
melanoma
Source Database
CIViC Evidence
Description
In this Phase III trial (coBRIM, NCT01689519) of 495 V600 mutant melanoma patients, 56 had V600K mutation. 32 patients were treated with vemurafenib and placebo, and 24 were treated with vemurafenib and cobimetinib and tested for progression free survival. 17 of 32 monotherapy group patients had an event with median progression free survival of 5.3 months. In the combination group 4 of 24 patients had an event with median progression-free survival not met, however, when in combination with other V600 mutations median progression-free survival was 9.9 months with combination treatment. Median time to followup for the whole cohort was 7.3 months. Hazard Ratio for progression or death was 0.27 (0.09-0.81).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/6965
Gene URL
https://civic.genome.wustl.edu/links/genes/5
Variant URL
https://civic.genome.wustl.edu/links/variants/563
Rating
4
Evidence Type
Predictive
Disease
Melanoma
Evidence Direction
Supports
Drug
Trametinib,Dabrafenib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
25265494
Drugs
Drug NameSensitivitySupported
DabrafenibSensitivitytrue
TrametinibSensitivitytrue