Annotation Detail

Information
Associated Genes
GNAQ
Associated Variants
GNAQ Q209
GNAQ Q209
Associated Disease
uveal melanoma
Source Database
CIViC Evidence
Description
101 patients with metastatic uveal melanoma were randomized 1:1 to receive selumetinib or chemotherapy. Median PFS among patients randomized to chemotherapy was 7 weeks (95% CI, 4.3-8.4 weeks; median treatment duration, 8 weeks; interquartile range [IQR], 4.3-16 weeks) vs. 15.9 weeks with selumetinib (95% CI, 8.4-21.1 weeks; median treatment duration, 16.1 weeks; IQR, 8.1-25.3 weeks) (hazard ratio, 0.46; 95% CI, 0.30-0.71; P < 0.001). Most patients (80/96 evaluable harbored a mutation in exon 5 of GNAQ or GNA11) but PFS benefit from Selumetinib compared to chemotherapy was greater in the GNAQ and GNA11 wild-type population (25.9 weeks [range, 3.7-40.4 weeks] vs 15.4 weeks [range, 8.1-16.9 weeks]). However, PFS was still better with Selumetinib than chemotherapy in the GNA mutant population (hazard ratio 0.55, 95% CI, 0.34-0.87; P = 0.01). The difference was explained by potential GNAQ or GNA11 mutations outside of exon 5 in the GNA wild-type population. Another three mutations in exon 4 were retrospectively identified in the wild-type population and one had a major response.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1213
Gene URL
https://civic.genome.wustl.edu/links/genes/2317
Variant URL
https://civic.genome.wustl.edu/links/variants/507
Rating
3
Evidence Type
Predictive
Disease
Uveal Melanoma
Evidence Direction
Does Not Support
Drug
Selumetinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
24938562
Drugs
Drug NameSensitivitySupported
SelumetinibSensitivityfalse