Annotation Detail

Information
Associated Genes
GNAQ
Associated Variants
GNAQ MUTATION
GNAQ MUTATION
Associated Disease
uveal melanoma
Source Database
CIViC Evidence
Description
Patients with metastatic melanoma (n=77; 48 cutaneous, 23 uveal, 6 mucosal) were enrolled in a phase II randomised discontinuation trial assessing cabozantinib. Patients received 100 mg cabozantinib daily for 12 weeks. Patients with stable disease (SD; RECIST; n=26) were randomly assigned to cabozantinib (n=13) or placebo (n=13). In the uveal melanoma cohort, 61% of patients (14/23, 61%) had SD at week 12. 9 patients had either a GNAQ (n=5) or GNA11 (n=4) mutation; only 10 patients were analyzed. Patients with GNAQ mutations remained on the study treatment from 1.4-10.3 months. The median PFS for the 23 patients with uveal melanoma was 4.8 months (41% PFS at 6 months) and median OS was 12.6 months. In the entire cohort, median overall PFS was 3.8 months (33% PFS at 6 months). After randomisation, median PFS for cabozantinib patients was 4.1 months and 2.8 months for placebo (HR 0.59, p=0.284).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/5068
Gene URL
https://civic.genome.wustl.edu/links/genes/2317
Variant URL
https://civic.genome.wustl.edu/links/variants/505
Rating
2
Evidence Type
Predictive
Disease
Uveal Melanoma
Evidence Direction
Supports
Drug
Cabozantinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
28103611
Drugs
Drug NameSensitivitySupported
CabozantinibSensitivitytrue