Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK EML4-ALK C1156Y–L1198F
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- Case report of a patient with metastatic ALK-rearranged NSCLC. After developing resistance to first and second line ALK inhibitors mediated by a C1156Y mutation, the patient had a partial response with the third generation ALK-inhibitor lorlatinib. The patient progressed on lorlatinib after 8 months, at which point whole exome sequencing revealed an EML4-ALK C1156Y–L1198F double mutation. In vitro, the double mutation was resistant to lorlatinib but sensitive to crizotinib. The patient was started on crizotinib again and had a clinical response that lasted for 6 months.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/843
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/352
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Lorlatinib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 26698910
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Lorlatinib | Resitance or Non-Reponse | true |