Palbociclib 125 mg Dose Feasible For Well-Differentiated, Dedifferentiated Liposarcoma

Progression-free survival and toxicity results support low palbociclib dose for advanced well-differentiated or dedifferentiated liposarcoma

medwireNews: Reducing palbociclib dose intensity may balance activity and side effects in patients with advanced well-differentiated or dedifferentiated liposarcoma (WD/DDLS), phase II trial results suggest.

An earlier study found that the selective CDK4 and CDK6 inhibitor had clinical benefit in this patient population when given at a dose of 200 mg/day for 14 days on a 21-day cycle but that the regimen also caused moderate haematological toxicity, explain Mark Dickson, from Memorial Sloan Kettering Cancer Center in New York, USA, and co-workers.

The current study, published in a brief report in JAMA Oncology, tested palbociclib in 60 patients with advanced WD/DDLS and RECIST measurable disease at a dose of 125 mg/day for 21 days over a 28-day cycle.

The first 30 patients had all received at least one systemic chemotherapy regimen, such as doxorubicin or gemcitabine , although 22 of the subsequent 30 patients in an expansion cohort were naïve to systemic treatment.

At 12 weeks, 14 of the first 28 patients had progression-free survival (PFS), thus meeting the trial’s primary endpoint, rising to 57.2% of the 59 evaluable participants. Median PFS was 17.9 weeks and there was no significant difference in the PFS of patients who had and had not received prior systemic treatment.

“Palbociclib was generally well tolerated with asymptomatic reversible neutropenia as the most common adverse effect”, the researchers report, with grade 3 and 4 events occurring in 33% and 3%, respectively.

Grade 3 anaemia affected 22% of patients, and grade 3 and 4 thrombocytopenia 5% and 2%, respectively. Just three patients developed haematological side effects resulting in a dose reduction to 100 mg, with one patient receiving a further reduction to 75 mg.

One patient achieved a complete response that lasted over 2 years, with five other patients showing tumour shrinkage.

And noting that biopsy samples from nine patients showed that clinical benefit was related to downregulation of MDM2, a marker previously linked to palbociclib response, the team concludes: “These data will be crucial to establishing a potential biomarker which could predict which patients may benefit from CDK4 inhibitors.”


Dickson MA, Schwartz GK, Keohan ML, et al. Well-differentiated or dedifferentiated liposarcoma treated with CDK4 inhibitor palbociclib. A phase 2 clinical trial. JAMA Oncol 2016; Advance online publication 28 April. doi:10.1001/jamaoncol.2016.0264

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