Annotation Detail

Information
Associated Genes
ERBB2
Associated Variants
ERBB2 AMPLIFICATION ( ENST00000269571.10 )
ERBB2 AMPLIFICATION ( ENST00000269571.10 )
Associated Disease
Her2-receptor positive breast cancer
Source Database
CIViC Evidence
Description
LUX-Breast 1 is a phase 3 trial (NCT01125566) which enrolled 508 patients with metastatic HER2 positive BC who had progressed after adjuvant or first-line trastuzumab. It was thought that the wider range of ErbB family blocking and irreversible properties of afatinib could be beneficial in trastuzumab resistant cancer cells, since ErbB family members are thought to play a role in trastuzumab resistance. Primary endpoint was intention-to-treat group PFS. 339 patients were assigned to afatanib + vinorelbine and 169 to trastuzumab + vinorelbine. Recruitment was stopped prematurely when it was deemed unlikely that the increased PFS would be seen in the afatinib group. Median PFS was 5.5 months in the afatinib group and 5.6 months in the trastuzumab group. Afatanib plus vinorelbine was less well tolerated than trastuzumab plus vinorelbine, and the authors conclude that trastuzumab remains the best choice for treatment of trastuzumab-progressed HER2 positive metastatic BC.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1012
Gene URL
https://civic.genome.wustl.edu/links/genes/20
Variant URL
https://civic.genome.wustl.edu/links/variants/306
Rating
4
Evidence Type
Predictive
Disease
Her2-receptor Positive Breast Cancer
Evidence Direction
Does Not Support
Drug
Afatinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
26822398
Drugs
Drug NameSensitivitySupported
AfatinibSensitivityfalse