Annotation Detail

Information
Associated Genes
ROS1
Associated Variants
ROS1 REARRANGEMENT ROS1 REARRANGEMENT
Associated Disease
lung adenocarcinoma
Source Database
CIViC Evidence
Description
Case report of a 77-year old male patient with lung adenocarcinoma (T2aN1M0, stage IIA) without EGFR, KRAS, or BRAF mutations, and no ALK gene rearrangement. CD72-ROS1 was identified in sequencing after progression on chemotherapy. Crizotinib at 250 mg orally twice daily led to resolution of metastatic disease. The patient remained disease-free for 13 months when a CT-scan showed a relapse with two nodules in the right lower lobe. Stereotactic radiation therapy, gamma knife radiosurgery, and ipilimumab did not lead to a relevant response (new pleural nodules, new intracranial metastases). The patient next received ceritinib on a “Signature Trial" for tumors with aberrations in ALK or ROS1 that are treated with oral ceritinib (LDK378) at 750 mg daily (NCT02186821). Restaging scans after two cycles showed a partial response confirmed after four cycles (56% decrease) per RECIST1.1. MRI showed that his brain metastases decreased as well.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1248
Gene URL
https://civic.genome.wustl.edu/links/genes/4941
Variant URL
https://civic.genome.wustl.edu/links/variants/269
Rating
1
Evidence Type
Predictive
Disease
Lung Adenocarcinoma
Evidence Direction
Supports
Drug
Ceritinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
26917690
Drugs
Drug NameSensitivitySupported
CeritinibSensitivitytrue