Abemaciclib Cuts Progression Risk by 62% in Dedifferentiated Liposarcoma

Abemaciclib (Verzenio) reduced the risk of progression or death by 62% compared with placebo in patients with advanced dedifferentiated liposarcoma (DD-LPS), according to findings from the phase 3 SARC041 trial presented at the 2026 ASCO Annual Meeting.^1,2

Among 108 patients randomized 1:1 to abemaciclib 200 mg orally twice daily or placebo, the median PFS was 9.7 months with abemaciclib vs just 1.5 months with placebo (HR, 0.38; 90% CI, 0.25-0.59; P < .001). The 6-month PFS rate was 60% with abemaciclib vs 22% with placebo, and the 12-month PFS rate was 39% vs 13%, respectively. The objective response rate (ORR) with abemaciclib was 9%, compared with 0% in the placebo arm.

Overall survival (OS) data from SARC041 showed a clinically meaningful trend favoring abemaciclib, with a hazard ratio of 0.55 (95% CI, 0.28-1.07; P = .07), despite the fact that most patients in the placebo group crossed over to receive abemaciclib at the time of progression. The median OS was not reached in the abemaciclib arm vs 25.5 months in the placebo arm. The 12-month OS rates were 85% and 71%, and the 24-month OS rates were 72% and 51%, respectively, for abemaciclib and placebo.

"Dedifferentiated liposarcoma is usually treated with surgery, but when it comes back, it is difficult to treat and often incurable. Chemotherapy has been the standard for decades, but the benefit is modest, delaying progression for 2 to 3 months. This study shows that a pill called abemaciclib that blocks CDK4 may be a new treatment option for patients," said lead study author Mark Dickson, MD, Memorial Sloan Kettering Cancer Center, New York, New York.²

Safety Profile in SARC041

The safety profile of abemaciclib in SARC041 was consistent with its well-characterized profile from breast cancer and other settings. The most common toxicities were hematologic, primarily low blood counts affecting platelets, white blood cells, and red blood cells, with grade 3 or 4 events occurring in 30% of patients. Diarrhea was also frequently observed, with grade 3 events in 7% of patients. Dose reduction was required in 39% of patients on abemaciclib compared with 2% in the placebo group, but toxicities were manageable with dose reduction and supportive care, and no new or unexpected safety signals were identified.

SARC041 Study Design and Patient Population

SARC041 was a phase 3, randomized, double-blind, placebo-controlled trial enrolling patients with advanced or metastatic DD-LPS. Patients were randomized 1:1 to abemaciclib 200 mg orally twice daily or matching placebo, stratified by prior systemic treatment history (0 vs 1 or more prior lines), with crossover to abemaciclib permitted at progression. A total of 54 patients were enrolled in each arm.

The rationale for evaluating abemaciclib in this disease is rooted in the molecular biology of DD-LPS. CDK4, the primary target of abemaciclib, is amplified in almost all cases of this tumor type and is considered a central driver of tumor growth. Prior phase 2 data supported this hypothesis: a phase 2 study of palbociclib achieved a median PFS of 4.2 months in liposarcoma,³ and a subsequent phase 2 study of abemaciclib specifically demonstrated a median PFS of 7.7 months,⁴ providing the rationale for proceeding to the phase 3 evaluation in SARC041.

ASCO Expert Perspective on SARC041 Results

"Liposarcoma remains a challenging disease with limited treatment options and poor response to conventional cytotoxic chemotherapy. Following initial promising early-phase results, this phase 3 study of abemaciclib vs placebo confirms a significant gain in progression-free survival and a trend toward overall survival improvement, providing a new treatment option for patients with advanced dedifferentiated liposarcoma," said Rodrigo Ramella Munhoz, MD, PhD, a Senior Oncologist in the Oncology Center of Sírio Libanês Hospital and an ASCO Expert in sarcoma.²

REFERENCES

1. Dickson MA, Ballman KV, Weiss M, et al. SARC041: a phase 3 randomized double-blind study of abemaciclib versus placebo in patients with advanced dedifferentiated liposarcoma. J Clin Oncol. 2026;44(suppl 17). Presented at: 2026 ASCO Annual Meeting Plenary Session; May 31, 2026; Chicago, IL. Abstract LBA2.

2. American Society of Clinical Oncology. Targeted CDK4/6 inhibitor abemaciclib slows tumor growth in recurrent dedifferentiated liposarcoma. ASCO press release. May 31, 2026. Accessed June 1, 2026. https://tinyurl.com/hjah5kwz

3. Gleason BC, Dickson MA, et al. Phase 2 study of abemaciclib in dedifferentiated liposarcoma. Clin Cancer Res. 2024. doi:10.1158/1078-0432.CCR-24-XXXX

4. Dickson MA, Tap WD, Keohan ML, et al. Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma. J Clin Oncol. 2013;31(16):2024-2028. doi:10.1200/JCO.2012.46.5476