Liposarcoma Updates from ASCO Annual Meeting

By Catherine Wilbur, MD & Christian Meyer, MD, PhD
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital

Each year, the American Society of Clinical Oncology (ASCO) Annual Meeting offers the opportunity to share cutting-edge research, explore novel therapeutic strategies and engage in multidisciplinary collaboration. Importantly, this meeting fosters connections between patient advocates, clinicians, and researchers, accelerating the translation of scientific discoveries into clinical practice. This is particularly crucial for rare cancer types, such as liposarcoma.

Liposarcoma (LPS) is a rare cancer type originating from lipocytes or fat cells. It is one of the more common subtypes of sarcoma, accounting for about 20% of all sarcomas. LPS arises commonly in the abdominal/pelvic area or the extremities and trunk. There are multiple different subtypes of LPS, including well-differentiated, dedifferentiated, myxoid and pleomorphic. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are the most common subtypes. Standard of care for localized WDLPS and DDLPS includes wide surgical resection. Perioperative chemotherapy is an area of active investigation with the field and is considered for patients with DDLPS depending on the location of the tumor and risk of recurrence. Anthracycline-based chemotherapy is considered first-line treatment for patients with advanced, unresectable, or Stage IV (metastatic) DDLPS.

ASCO Annual Meeting 2025 brought us exciting new research findings and updates about liposarcoma.

1. Long-term follow-up of palbociclib for the treatment of WDLPS and DDLPS
   Gene amplification of mouse double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) are present in nearly all well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) and have become attractive therapeutic targets. Previously, two phase II clinical trials assessed the use of palbociclib, a CDK4 and CDK6 inhibitor, for the treatment of WDLPS and DDLPS. Due to the clinical activity of palbociclib for WDLPS and DDLPS, palbociclib is now listed in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of these tumor types. The long-term follow-up of approximately 8.5 years from those clinical trials was presented. Palbociclib in advanced WDLPS and DDLPS demonstrated median progression-free survival (PFS) of approximately 18 weeks and median overall survival (OS) of 24–26 months. Patients with pure WDLPS had longer PFS, but OS did not differ significantly by subtype of LPS. This long-term follow-up shows that palbociclib was well tolerated and provides an alternative for patients who cannot tolerate standard chemotherapy. This data reaffirms the role of palbociclib in advanced WDLPS and DDLPS, though outcomes remain modest and highlight the need for novel treatment strategies.

2. New treatment strategy with low-dose combination chemotherapy and immunotherapy.
   In the setting of advanced or metastatic liposarcoma, chemotherapy is the primary treatment. Anthracycline-based chemotherapy, such as doxorubicin, is often used as first-line treatment. An alternative regimen utilizes the combination of gemcitabine and docetaxel. A phase II clinical trial investigated the combination of multiple chemotherapies, including gemcitabine, doxorubicin and docetaxel, in combination with an immunotherapy called nivolumab.
   The chemotherapy agents were given in lower doses than what is standardly given. The study enrolled 11 patients with liposarcoma and 30 patients with leiomyosarcoma, which is a cancer of smooth muscle. While only a limited number of patients with LPS were enrolled, the study showed promising results with approximately 20% of patients experiencing a decrease in size of their cancer and 87% of patients experiencing either a decrease or stability in the size of their tumors. The treatment was generally well-tolerated without unexpected side effects. Given the small number of liposarcoma patients in this trial, a larger clinical trial is needed to further investigate efficacy and safety, but this may be an effective treatment strategy in the future.

3. Further molecular insights for liposarcoma

   Changes in DNA, called gene fusions, play a significant role in how cancer develops, grows and behaves. Researchers used a technique called RNA sequencing to identify these gene fusions in different subtypes of liposarcoma. Biopsy samples taken from 150 patients with liposarcoma were analyzed. The results confirmed the presence of known gene fusions and revealed new gene fusion hotspots. This study improves our understanding of how liposarcoma develops, increases our diagnostic accuracy, and may lead to more personalized treatments in the future.

4. Updates on current clinical trials enrolling patients with liposarcoma

   Two national clinical trials are being conducted through the National Cancer Institute’s (NCI) Experimental Therapeutics Clinical Trials Network and are enrolling patients with liposarcoma. The first clinical trial is entitled “Phase I/II study to evaluate the feasibility and efficacy of sequential abemaciclib and gemcitabine treatment in patients with retinoblastoma (Rb)-positive leiomyosarcoma (LMS) and dedifferentiated liposarcoma (DDLPS).” Eligible patients must have a protein called retinoblastoma (Rb) expressed in their tumor. The first part of the trial aims to find the best dose of abemaciclib, a CDK4 and CDK6 inhibitor, and gemcitabine, a standard chemotherapy agent, when given in combination. The second phase of the trial aims to determine how well abemaciclib and gemcitabine controls the cancer compared to standard chemotherapy with gemcitabine and docetaxel. The second clinical trial is entitled “Phase I study of peposertib and liposomal doxorubicin for advanced or metastatic leiomyosarcoma and other sarcomas”. This trial is enrolling patients with advanced or metastatic DDLPS during the first portion of the clinical trial only. The trial is evaluating liposomal doxorubicin in combination with peposertib, a targeted therapy that blocks one way that cancer cells repair themselves after being damaged. The main goal of the study is to find the safest dose of peposertib that can be given with liposomal doxorubicin and to see if this combination could help control the cancer.

   Overall, the findings from this year’s ASCO Annual Meeting mark important steps forward in the fight against liposarcoma and bring hope for better treatments and brighter outcomes for patients living with liposarcoma.