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The CDK4/6 inhibitor abemaciclib significantly delays progression of advanced dedifferentiated liposarcoma, in findings that experts said open up a new treatment option for patients who currently have few.

Among 108 patients in a phase 3 trial, abemaciclib extended median progression-free survival to nearly 10 months, compared to 1.5 months with placebo, according to findings presented at the American Society of Clinical Oncology (ASCO) 2026 annual meeting.

“This is the first positive phase 3 clinical trial ever in dedifferentiated liposarcoma,” lead researcher Mark Dickson, MD, of Memorial Sloan Kettering Cancer Center in New York City, said during a press briefing.

Abemaciclib (Verzenio), already widely used in breast cancer, now offers a new treatment option for patients with this rare disease, Dickson said.

Rodrigo Munhoz, MD, a medical oncologist at Hospital Sírio-Libanês in São Paulo, Brazil, agreed.

“Abemaciclib may become the new standard of care for patients with recurrent advanced liposarcoma not amenable to surgical resection,” said Munhoz, who was not involved in the trial.

Sarcomas are relatively rare, accounting for about 1% of all cancers in the US, with dedifferentiated liposarcoma being one of the more common subtypes. For years, the standard of care for the disease has been surgery followed by surveillance, as second-line chemotherapy offers limited benefit, Dickson said.

But research over the past 20 years has shown that in nearly all cases of dedifferentiated liposarcoma, the oncogene CDK4 is amplified, driving the cancer’s growth. That made testing CDK4 inhibition a “very rational strategy,” Dickson said.

In an early study of patients with liposarcomas, Dickson and colleagues found that the CDK4/6 inhibitor palbociclib yielded a median progression-free survival of just over 4 months. That’s modestly better than what’s seen with FDA-approved second-line chemotherapies, where progression-free survival is about 2 months, Dickson noted.

Abemaciclib differs from other CDK4/6 inhibitors: It’s more selective for CDK4 — which “gives you the antitumor effect in liposarcoma,” Dickson said — while its weaker activity against CDK6 reduces the risk for neutropenia and allows continuous daily dosing.

In a phase 2 study of patients with progressing dedifferentiated liposarcoma, Dickson’s team found that abemaciclib extended median progression-free survival to 7.7 months.

That led to the new trial, SARC041, which was conducted through the nonprofit Sarcoma Alliance for Research through Collaboration at nine US academic centers.

The trial enrolled 108 patients with recurrent or metastatic dedifferentiated liposarcoma and any number of prior treatments. Patients were randomized 1:1 to receive either abemaciclib 200 mg or placebo twice daily. Those who progressed on placebo could cross over to the intervention group. 

Median progression-free survival, the primary endpoint, was 9.7 months in the abemaciclib group, compared with 1.5 months in the placebo group (hazard ratio [HR], 0.38; P < .001). 

At 6 months, 60% of abemaciclib-treated patients were progression-free, compared with 22% in the placebo group. At 12 months, these figures were 39% and 13%, respectively.

A secondary endpoint was overall survival. For patients who started on abemaciclib, median overall survival has not yet been reached, while in the placebo group it was 25.5 months (HR, 0.55; P = .07).

Dickson noted that the difference in overall survival was apparent even though most patients randomized to placebo (85%) crossed over to receive abemaciclib.

Side effects were in line with what’s seen with CDK4/6 inhibitors in breast cancer treatment, Dickson said. About 30% of patients on abemaciclib developed grade 3 or 4 cytopenias, while 7% had grade 3 diarrhea.

Those adverse events were managed with supportive care and/or dose reductions, Dickson said, with 39% of patients in the abemaciclib group needing dose reductions vs 2% in the placebo group.

Munhoz noted that compared with standard chemotherapy, the toxicity profile with the CDK4/6 inhibitor looks better.

An exploratory analysis looked at outcomes according to prior therapy. About half of patients in the trial had received no prior treatment, Dickson said, while the other half had received at least one. And it appeared that timing was key: Median progression-free survival exceeded 16 months when abemaciclib was given first-line vs 5.4 months for later lines.

During the press conference, Dickson was asked to explain the use of a placebo control instead of chemotherapy.

He replied that patients with large-volume, symptomatic disease were ineligible for the trial, as they should start first-line chemotherapy. The trial, Dickson added, was designed as a “broad tent,” offering abemaciclib to patients at first relapse, if appropriate, and also to those who had exhausted all standard options.

Looking ahead, Dickson brought attention to the emergence of even more selective CDK4 inhibitors for patients with breast cancer. He said it would be “incredibly interesting” to evaluate those drugs in managing liposarcoma, too.

SARC041 was an investigator-initiated trial funded by abemaciclib manufacturer Eli Lilly. Dickson reported institutional research funding from Eli Lilly and other sources. Munhoz disclosed relationships with Bristol-Myers Squibb, MSD, Novartis, and others.