Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.

[dedifferentiated liposarcoma]

CDK 4 is amplified in > 90 % of well-differentiated (WDLS ) and dedifferentiated liposarcomas (DDLS ). The selective cyclin-dependent kinase 4 (CDK 4 )/CDK 6 inhibitor PD 0332991 inhibits growth and induces senescence in cell lines and xenografts . In a phase I trial of PD 0332991 , several patients with WDLS or DDLS experienced prolonged stable disease . We performed an open -label phase II study to determine the safety and efficacy of PD 0332991 in patients with advanced WDLS /DDLS .Patients age â‰¥ 18 years experiencing disease progression while receiving systemic therapy before enrollment received PD 0332991 200 mg orally once per day for 14 consecutive days in 21 -day cycles . All were required to have CDK 4 amplification by fluorescence in situ hybridization and retinoblastoma protein (RB ) expression by immunohistochemistry (â‰¥ 1 +). The primary end point was progression-free survival (PFS ) at 12 weeks , with 12 -week PFS of â‰¥ 40 % considered promising and â‰¤ 20 % not promising . If â‰¥ nine of 28 patients were progression free at 12 weeks , PD 0332991 would be considered active .We screened 48 patients (44 of 48 had CDK 4 amplification ; 41 of 44 were RB positive ). Of those , 30 were enrolled , and 29 were evaluable for the primary end point . Grade 3 to 4 events included anemia (17 %), thrombocytopenia (30 %), neutropenia (50 %), and febrile neutropenia (3 %). At 12 weeks , PFS was 66 % (90 % CI , 51 % to 100 %), significantly exceeding the primary end point . The median PFS was 18 weeks . There was one partial response .Treatment with the CDK 4 inhibitor PD 0332991 was associated with a favorable progression-free rate in patients with CDK 4 -amplified and RB-expressing WDLS /DDLS who had progressive disease despite systemic therapy .

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Diseases presenting "open-label phase" symptom

dedifferentiated liposarcoma

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