Annotation Detail

Information
Associated Genes
RET
Associated Variants
RET UNKNOWN
RET FUSION
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. The clinical activity of alectinib in patients with RET-rearranged NSCLC has not yet been reported. 4 patients with metastatic RET-rearranged NSCLC were identified. 3 of 4 had received prior RET TKIs, including cabozantinib and experimental RET inhibitors. We observed two (50%) objective radiographic responses after treatment with alectinib (one confirmed and one unconfirmed), with durations of therapy of 6 months and more than 5 months (treatment ongoing). Notably, one of these two patients had his dose of alectinib escalated to 900 mg twice daily and had clinical improvement in central nervous system metastases. In addition, one patient (25%) experienced a best response of stable disease lasting approximately 6 weeks. A fourth patient who was RET TKI-naive had primary progression while receiving alectinib.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/4850
Gene URL
https://civic.genome.wustl.edu/links/genes/42
Variant URL
https://civic.genome.wustl.edu/links/variants/1687
Rating
3
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Alectinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
27544060
Drugs
Drug NameSensitivitySupported
AlectinibSensitivitytrue