Clinical Summary:

• Design/Population: The phase 3 SARC041 trial randomized patients with recurrent or metastatic dedifferentiated liposarcoma to receive abemaciclib or placebo, with crossover to open-label abemaciclib allowed after progression on placebo.
• Key Outcomes: Abemaciclib significantly improved progression-free survival compared with placebo, with an encouraging trend toward improved overall survival. Objective responses were uncommon but favored abemaciclib, and no new safety signals were observed.
• Clinical Relevance: Abemaciclib may provide a new systemic treatment option for dedifferentiated liposarcoma, a disease with limited effective therapies, supporting CDK4 inhibition as a clinically meaningful strategy in this biomarker-driven sarcoma subtype.

Mark Dickson, MD, Memorial Sloan Kettering Cancer Center, New York, New York, discusses results from the phase 3 SARC041 trial, which randomized patients with recurrent or metastatic dedifferentiated liposarcoma to receive either abemaciclib or placebo. 

Results demonstrated that abemaciclib significantly improved progression-free survival (PFS) with favorable trends toward improved overall survival (OS), and no new safety concerns. These findings support abemaciclib as a promising new therapeutic option in this patient population. 

Dr Dickson presented these results during the plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

Transcript: 

Hi, I'm Mark Dickson, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York. I'm here today at ASCO presenting the results of SARC041. This is a phase 3, randomized, placebo-controlled, multicenter study in a relatively rare disease called dedifferentiated liposarcoma.

Dedifferentiated liposarcoma is one of the more common soft tissue sarcomas in adults, with several thousand cases diagnosed each year in the United States. The usual approach is complete surgical resection followed by surveillance, and no adjuvant therapy has been proven to improve outcomes. Unfortunately, recurrences are common, and treatment options include repeat surgical debulking, which is ultimately palliative, or systemic therapy. Doxorubicin has remained a standard systemic therapy for more than 50 years, despite relatively low response rates and substantial toxicity.

Since the era of genomic sequencing, we've known that almost all dedifferentiated liposarcomas harbor high-level amplification of the oncogene cyclin-dependent kinase 4 (CDK4). As a result, we've been very interested in targeting this pathway. Many people are familiar with the CDK4/6 inhibitors palbociclib and abemaciclib in breast cancer. We previously tested both agents in phase 2 studies in dedifferentiated liposarcoma and selected abemaciclib for phase 3 evaluation. It has several potential advantages, including greater selectivity for CDK4 than CDK6, resulting in less neutropenia and allowing for continuous daily dosing, which may improve target inhibition in cancer cells.

The phase 3 SARC041 trial enrolled 108 patients at 9 cancer centers across the United States. Patients with recurrent or metastatic dedifferentiated liposarcoma were randomized to receive either abemaciclib or placebo. Patients assigned to placebo were permitted to cross over to open-label abemaciclib at the time of disease progression. The primary end point was progression-free survival.

The study met its primary end point. Median progression-free survival was 9.7 months with abemaciclib compared with 1.5 months with placebo, a highly statistically significant difference. Regarding secondary end points, the objective response rate by RECIST was 9% with abemaciclib and 0% with placebo.

Most interestingly, we also observed a difference in overall survival despite the fact that 85% of patients assigned to placebo later received abemaciclib through crossover. Median overall survival was 25.5 months in the placebo arm, while median overall survival in the abemaciclib arm has not yet been reached. This corresponded to a hazard ratio of 0.55 and a P value of .07.

The study enrolled patients across a broad range of treatment settings, including those who had received no prior systemic therapy as well as patients who had received multiple prior lines of chemotherapy. Our rationale was to make this potentially beneficial treatment available to as many patients as possible. For example, patients with a low-volume, asymptomatic retroperitoneal recurrence could reasonably enroll in a placebo-controlled first-line study rather than begin toxic chemotherapy such as doxorubicin. At the same time, heavily pretreated patients with limited standard treatment options were also appropriate candidates.

In a post hoc analysis, we examined progression-free survival among patients who received abemaciclib in the first-line setting compared with later-line therapy. Patients who received abemaciclib as first-line treatment achieved a progression-free survival of more than 16 months, which exceeds anything previously reported in this disease.

Overall, these findings represent the first positive phase 3 clinical trial in dedifferentiated liposarcoma and support abemaciclib as a promising new therapeutic option for patients with this CDK4-amplified sarcoma subtype.

Source:

Dickson MA, Ballman KV, Weiss MC, et al. SARC041: A phase 3 randomized double-blind study of abemaciclib versus placebo in patients with advanced dedifferentiated liposarcoma. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA2.