Annotation Detail

Information
Associated Genes
CDK4
Associated Variants
CDK4 AMPLIFICATION ( ENST00000257904.11 )
CDK4 AMPLIFICATION ( ENST00000257904.11 )
Associated Disease
liposarcoma
Source Database
CIViC Evidence
Description
More than 90% of well-differentiated or dedifferentiated liposarcomas (WD/DDLS) have CDK4 amplification. A prior phase 2 study demonstrated that treatment with palbociclib (200 mg/d for 14 days every 21 days) resulted in clinical benefit in WD/DDLS but moderate hematologic toxic effects. In this phase 2, nonrandomized, open-label clinical trial conducted at the Memorial Sloan Kettering Cancer Center, 60 patients 18 years and older with advanced WD/DDLS and measurable disease by RECIST 1.1 were enrolled from December 2011 to January 2014 and followed to March 2015. Patients received oral palbociclib at new dose scheme, 125 mg/d for 21 days in 28-day cycles. Progression-free survival at 12 weeks was 57.2% and overall median PFS was 17.9 weeks. There was 1 complete response. Toxic effects were primarily hematologic and included neutropenia (grade 3, n = 20 [33%]; grade 4, n = 2 [3%]) but no neutropenic fever. Compared to other dose scheme in PMID 23569312 with 200mg/d: 12week PFS 66%, overall median PFS 18 weeks.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/4841
Gene URL
https://civic.genome.wustl.edu/links/genes/13
Variant URL
https://civic.genome.wustl.edu/links/variants/553
Rating
3
Evidence Type
Predictive
Disease
Liposarcoma
Evidence Direction
Supports
Drug
Palbociclib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
27124835
Drugs
Drug NameSensitivitySupported
PalbociclibSensitivitytrue