Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK EML4-ALK C1156Y
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
Case report of a patient with metastatic ALK-rearranged NSCLC after progression under sequential crizotinib, ceritinib, HSP90 inhibitor AUY922 and chemotherapy followed by crizotinib again. Third generation ALK inhibitor lorlatinib led to a partial response that lasted for 8 months. The C1156Y mutation was confirmed in a sample prior to initial crizotinib (<7% of cells), following crizotinib treatment (~50% of cells) and following lorlatinib resistance (100% of cells). However, a second ALK mutation (C1156Y & L1198F) was detected in the lorlatinib resistant tumor.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/842
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/6
Rating
3
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Lorlatinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
26698910
Drugs
Drug NameSensitivitySupported
LorlatinibSensitivitytrue