Ibrance for liposarcoma- pro
In a single-center phase II trial reported in JAMA Oncology, Dickson et al found that changing the dose and schedule of palbociclib (Ibrance) from those in a previous phase II trial appeared to maintain activity while potentially reducing hematologic adverse effects in patients with advanced well-differentiated or dedifferentiated liposarcoma. In the previous study, a palbociclib regimen of 200 mg/d for 14 days every 21 days in 30 patients was associated with median progression-free survival of 18 weeks and excessive hematologic adverse events.
In the prior study, 60 patients were treated with palbociclib at 125 mg daily for 21 of every 28 days. Progression-free survival at 12 weeks was 57.2% (95% confidence interval [CI] = 42.4%–68.8%), and median progression-free survival was 17.9 weeks (95% CI = 11.9–24.0 weeks). One complete response lasting more than 2 years was observed.
Hematologic adverse events included grade 3 and 4 neutropenia in 33% and 3%, grade 3 anemia in 22%, and grade 3 and 4 thrombocytopenia in 5% and 2%. No neutropenic fever was observed. Dose was reduced to 100 mg/d in three patients and to 75 mg/d in one patient due to hematologic adverse events.
The investigators concluded: “In patients with advanced well-differentiated or dedifferentiated liposarcoma, treatment with palbociclib was associated with a favorable [progression-free survival] and occasional tumor response. This dose and schedule appears active and may have less toxic effects than 200 mg for 14 days.”
However, palbociclib is an a clinical trial,NCT01209598, which says: “Palbociclib is an investigational drug. An investigational drug is a medication that has not been approved for marketing by the Food and Drug Administration (FDA). Palbociclib blocks a protein called CDK4 which is part of a pathway in liposarcoma cells that is over-active. The investigators hope that blocking CDK4 will shut down this pathway in the liposarcoma cells and stop tumors from growing. Palbociclib is an oral medication.”. It is, therefore, not medically necessary.
Dickson MAet al, Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial.
JAMA Oncol. 2016 Jul 1;2(7):937-40.
Audrey Laroche-Clar et aly, Combined targeting of MDM2 and CDK4 is synergistic in dedifferentiated liposarcomas. Journal of Hematology & Oncology201710:123