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 the Phase I study PROFILE 1001 (NCT00585195), a recommended crizotinib dose of 250 mg twice daily for 28 day cycles was established. Among 1,500 advanced NSCLC patients who were screened for ALK-rearrangement using a break-apart FISH assay, 82 patients were eligible for crizotinib treatment. Overall response rate was 57%, with 46 partial responses and one complete response. Since crizotinib inhibits MET, 33 patients with available tissue were screened for MET amplification and were found negative, further indicating that patient response was due to ALK inhibition. 31 patients were tested via RT-PCR for known EML4-ALK fusions, and 13 were shown to have EML4-ALK variant 1, four cases had variant 3, and one instance of variants 2, 3b and 5 were seen. 9 were unidentified, suggesting other fusion partners in these instances. On the basis of this and a Phase II study, accelerated approval for crizotinib in ALK-positive advanced NSCLC was granted.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1187
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/499
Rating
5
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Crizotinib
Evidence Level
A
Clinical Significance
Sensitivity/Response
Pubmed
20979469
Drugs
Drug NameSensitivitySupported
CrizotinibSensitivitytrue