Annotation Detail

Information
Associated Genes
PIK3CA
Associated Variants
PIK3CA p.Glu542Lys (p.E542K) ( ENST00000643187.1, ENST00000263967.4 )
PIK3CA p.Glu542Lys (p.E542K) ( ENST00000263967.4, ENST00000643187.1 )
Associated Disease
breast cancer
Source Database
CIViC Evidence
Description
In a phase 3 trial, 572 patients with hormone receptor positive, HER2 receptor negative advanced breast cancer who previously received endocrine therapy were allocated to alpelisib plus fulvestrant or placebo plus fulvestrant. Patients were enrolled into two cohorts on the basis of tumor-tissue PIK3CA mutation status (N=341). PIK3CA mutation was determined according to the presence or absence of any hot spot mutation in the C2, helical, and kinase domains of PI3K (corresponding to exon 7, 9, and 20, respectively). In the cohort of patients with PIK3CA-mutated cancer, PFS was 11 months in the alpelisib-fulvestrant group, as compared with 5.7 months in the placebo-fulvestrant group (HR 0.65, p<0.001). In the cohort without PIK3CA-mutated cancer, the HR was 0.85. Analyses of PFS according to mutation types showed consistent benefit of treatment with alpelisib–fulvestrant across prespecified subgroups, including E542K (N=60, HR 0.60, 95% CI 0.29-1.23), E545X, and H1047X.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7315
Gene URL
https://civic.genome.wustl.edu/links/genes/37
Variant URL
https://civic.genome.wustl.edu/links/variants/103
Rating
3
Evidence Type
Predictive
Disease
Breast Cancer
Evidence Direction
Supports
Drug
Alpelisib,Fulvestrant
Evidence Level
A
Clinical Significance
Sensitivity/Response
Pubmed
31091374
Drugs
Drug NameSensitivitySupported
AlpelisibSensitivitytrue
FulvestrantSensitivitytrue