Annotation Detail

Information
Associated Genes
KIT
Associated Variants
KIT p.Asp821Tyr (p.D821Y) ( ENST00000412167.7, ENST00000689832.1, ENST00000288135.6, ENST00000687246.1, ENST00000686011.1, ENST00000687109.1, ENST00000687295.1, ENST00000689994.1, ENST00000690543.1, ENST00000692783.1 )
KIT p.Asp821Tyr (p.D821Y) ( ENST00000288135.6, ENST00000412167.7, ENST00000686011.1, ENST00000687109.1, ENST00000687246.1, ENST00000687295.1, ENST00000689832.1, ENST00000689994.1, ENST00000690543.1, ENST00000692783.1 )
Associated Disease
gastrointestinal stromal tumor
Source Database
CIViC Evidence
Description
This retrospective study of a phase 2 clinical trial (NCT01068769) examined regorafenib safety and efficacy in advanced gastrointestinal stromal tumor (GIST) patients refractory to at least imatinib and sunitinib. Three patients whose GIST harbored KIT D820Y experienced clinical benefit (defined as complete response, partial response, stable disease >16 weeks) in response to regorafenib. One patient remained on study without disease progression for >11 months, one patient developed disease progression at 5.7 months, and the other patient underwent surgical removal of all residual disease after 7 months, but continued on regorafenib. Immunoblotting of matched pre- and post- treatment GIST biopsies from these patients demonstrated decreased levels of KIT phosphorylation in response to regorafenib.
Rating
2
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/4589
Gene URL
https://civic.genome.wustl.edu/links/genes/29
Variant URL
https://civic.genome.wustl.edu/links/variants/986
Evidence Type
Predictive
Disease
Gastrointestinal Stromal Tumor
Evidence Direction
Supports
Drug
Regorafenib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
22614970
Drugs
Drug NameSensitivitySupported
RegorafenibSensitivitytrue