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
In a phase II randomized trial we evaluated two regimens of Brigatinib in Crizotinib-refractory ALK-pos. NSCLC. They were randomly assigned (1:1) to oral Brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg. Of 222 patients enrolled (arm A: n = 112, arm B: n = 110), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. ORR was 45 (arm A) and 54% (B). Investigator-assessed median PFS was 9.2 months (A) and 12.9 months (B). Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11/26, A) and 67% (12/18, B). Brigatinib yielded substantial whole-body and intracranial responses as well as robust PFS; 180 mg (with lead-in) showed consistently better efficacy than 90 mg, with acceptable safety.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/4835
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/499
Rating
4
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Brigatinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
28475456
Drugs
Drug NameSensitivitySupported
BrigatinibSensitivitytrue