Palbociclib: A novel and effective therapy for advanced liposarcoma

Myxoid liposarcomas are rare tumours associated with a high likelihood of recurrence and a dismal prognosis, even with multimodality therapy.¹ Despite its chemosensitivity, the options are limited beyond the conventional anthracycline and taxane-based chemotherapy regimens, with subsequent lines considered experimental.² CDK4 amplification is detected in 90% of liposarcomas, and the inhibitor palbociclib is part of the National Comprehensive Cancer Network (NCCN) guidelines.^2,3 We present a patient with chemotherapy-resistant myxoid liposarcoma that showed a considerable response to palbociclib.

In October 2022, a 47-year-old man, free of comorbid conditions and with good performance status, presented with a non-metastatic myxoid liposarcoma of FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) grade 2 located in his left thigh. He underwent resection with negative margins and received adjuvant radiotherapy. Two months later, in December 2022, he had a recurrence in the retroperitoneal region, which was resected. The patient defaulted to adjuvant chemotherapy. By May 2023, after 5 months, he developed metastases to the liver, lungs and multiple bones. He commenced gemcitabine with docetaxel combination chemotherapy, but after three cycles, he had disease progression. Subsequently, he was started on doxorubicin with ifosfamide chemotherapy, and underwent three cycles before encountering disease progression. Owing to financial constraints, he was unable to access chemotherapy options like eribulin and trabectedin, next-generation sequencing, or any targeted therapy. Consequently, he commenced generic palbociclib at a 125 mg dose for days 1–21 of a 28-day cycle. He had a considerable response upon CT scan evaluation after four cycles. He completed 6 months of treatment and had notable improvement in symptoms. In March 2023, 7 months into therapy with palbociclib, he developed disease progression. It is noteworthy that palbociclib kept the disease under control for over 6 months, whereas conventional chemo-therapy failed within less than 3 months.

We present this case to raise awareness among clinicians about a potentially valuable, cost-effective, less toxic and underutilized treatment approach for chemotherapy-resistant liposarcomas. While inhibition of the CDK4/6 pathway has been notably effective in liposarcomas, its application in other sarcomas such as leiomyosarcoma, osteosarcoma, rhabdomyosarcoma, and BCORCCNB3 fusion-positive sarcoma remains an area of active research.⁴ The role of CDK4/6 inhibitors requires further evaluation in prospective biomarker-guided trials in soft tissue sarcomas.