Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK ALK FUSIONS ALK ALK FUSIONS
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
This prospective Phase III study named Profile 1014 on NSCLC ALK-rearranged patients assessed intracranial disease control rate (IC-DCR) in the subset of patients entering the study with preexisting treated brain metastasis (tBM). IC-DCR was significantly improved in the tBM group given crizotinib (N=39) over chemotherapy (pemetrexed + cisplatin or carboplatin; N=40) at 12 weeks (85% vs. 45%, P<0.001), and at 24 weeks (56% vs. 25%, P=0.006). Progression free survival was also significantly improved with crizotinib over chemotherapy in the tBM subgroup (9.0 vs. 4.0 months; HR 0.40; P<0.001), where in the intent to treat population it was 10.9 vs. 7.0 months (HR 0.45; P<0.001), indicating that the difficult to treat BM population obtained benefit from crizotinib at both the brain and systemic level.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1201
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/499
Rating
4
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Crizotinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
27022118
Drugs
Drug NameSensitivitySupported
CrizotinibSensitivitytrue