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
In this Phase I trial (NCT01588028) in 47 patients, alectinib was assessed for its effectiveness in treating locally advanced or metastatic ALK-positive NSCLC that had progressed or been resistant to crizotinib treatment. ALK rearrangement was assessed via approved break apart FISH kit, and patients with asymptomatic CNS metastases were also included. Patients were divided into different cohorts receiving different doses of alectinib. In the 600 mg cohort (N=13), there were 4 confirmed partial responses, 3 unconfirmed partial responses and 3 instances of stable disease. Also, five of nine patients throughout the cohorts with measurable baseline CNS lesions showed partial response to alectinib. Cerebrospinal fluid levels of alectinib increased linearly with blood alectinib levels, indicating it effectively crossed the blood-brain barrier.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1279
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
Alectinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
25153538
Drugs
Drug NameSensitivitySupported
AlectinibSensitivitytrue