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 phase 3 trial named PROFILE 1014 (NCT01154140) compared crizotinib to established chemotherapy in first-line treatment for this disease. The study consisted of 343 patients with advanced or metastatic NSCLC that tested positive for ALK rearrangement via break-apart FISH assay, and had no prior systemic treatment. Patients were assigned in a 1:1 ratio to crizotinib (N=172) or pemetrexed with cisplatin or carboplatin (N=171). Progression free survival was significantly longer with crizotinib treatment than chemotherapy (10.9 vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% CI, 0.35 to 0.60;P<0.001), and objective response rate was higher with crizotinib treatment than chemotherapy (75% vs. 45%, P<0.001). Improvement in quality of life was also reported.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1199
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
25470694
Drugs
Drug NameSensitivitySupported
CrizotinibSensitivitytrue