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 two arm Phase III study named PROFILE 1007 (NCT00932893) was performed to assess crizotinib vs. established chemotherapy in non-small cell lung cancer patients positive for ALK rearrangement (assessed by break-apart FISH) with locally advanced or metastatic disease. 347 patients with disease progression after one round of platinum-based chemotherapy were randomized to receive crizotinib (N=173) or chemotherapy (N=174) consisting of pemetrexed in pemetrexed-naive patients and docetaxel for patients previously treated with pemetrexed. The primary endpoint - progression free survival (PFS) - was found to be significantly better for patients treated with crizotinib (median 7.7 months) than with chemotherapy (median 3.0 months) (hazard ratio for disease progression or death with crizotinib, 0.49; 95% CI, 0.37 to 0.64; P<0.001). Response rates were 65% for crizotinib treatment and 20% for chemotherapy (P<0.001). Improvements in quality of life were also reported.
Pubmed
23724913
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1198
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
Drugs
Drug NameSensitivitySupported
CrizotinibSensitivitytrue