SARC041 and the Future of Dedifferentiated Liposarcoma Treatment

Dedifferentiated liposarcoma is one of the most treatment-resistant soft tissue sarcomas, and for decades, patients have had few meaningful options beyond surgery. That may be changing. Pharmacy Times spoke with Mark A. Dickson, MD, associate attending physician at Memorial Sloan-Kettering Cancer Center, at the 2026 American Society of Clinical Oncology Annual Meeting about SARC041—the first phase 3 trial to demonstrate a clinically meaningful benefit with a CDK4/6 inhibitor in this rare and difficult-to-treat disease.

Pharmacy Times: Dedifferentiated liposarcoma is a disease most oncologists will see only a handful of times in their career. What drew you to rare sarcomas, and what does it feel like to work in a space where the patient population is small but the unmet need is enormous?

Mark A. Dickson, MD: My first interest in this area of cancer medicine grew during my fellowship when I was studying rare diseases—sarcoma, melanoma, and phase 1 studies. At that time, there weren't many targeted therapies or immunotherapies available, and we realized that to make any progress, we had to focus on specific disease subtypes with specific genetic drivers. This came about at the same time that sequencing was advancing, and we were learning about the mutations driving the different kinds of sarcoma. That's when we identified CDK4 amplification as a defining feature of dedifferentiated liposarcoma. It became an early-career focus for me—I started a phase 1 treatment in 2006 as a fellow, moved to phase 2 in 2010, and we've really been pushing at this for a long time. So it is incredibly rewarding to finally have a success.

Pharmacy Times: CDK4 amplification is one of the defining molecular features of dedifferentiated liposarcoma—so the rationale for testing a CDK4/6 inhibitor here has always made biological sense. What took so long for the field to get here, and what finally made SARC041 possible?

Dickson: We've done a series of phase 2 studies over the years—the first with palbociclib and subsequently with abemaciclib (Verzenio; Eli Lilly & Co). What we were really waiting for was to identify the optimal CDK4 inhibitor to advance into a phase 3 study. Abemaciclib is a more selective inhibitor of CDK4 versus CDK6, which means it causes less neutropenia and permits continuous daily dosing. That continuity of target suppression in the cancer cell, I believe, is important. The other factor was developing the infrastructure and resources through the SARC cooperative group to conduct a trial in a rare disease and accrue enough patients. The study opened in 2021, finished accrual in 2024, and now we have the results.

Pharmacy Times: CDK4/6 inhibitors in breast cancer have taught us a lot about resistance. What does the progression-free survival curve look like in SARC041, and are there early signals about who maintains benefit longest?

Dickson: There are early signals that a subset of patients may derive long-term benefit. We've seen patients with stable disease or partial responses lasting several years, both in the phase 2 study and trending in that direction in the phase 3 data. It's clear that not everyone benefits, but a meaningful minority can do extremely well for an extended period. We're looking very carefully at archival tissue—which we've obtained from nearly all phase 3 patients—to identify potential biomarkers of response. On the phase 2 side, we have tissue from surgically resected resistant liposarcoma, and we're beginning to understand resistance mechanisms. We published a paper about a year and a half ago on cyclin D amplification as one potential mode of resistance, and that work continues.

Pharmacy Times: The abemaciclib toxicity profile is well characterized in breast cancer. Did those signals look the same in a sarcoma population, or did this patient group tolerate the drug differently than what you'd expect from the breast cancer data?

Dickson: The toxicity profile was very similar to what you'd expect from the breast cancer experience—some myelosuppression, some diarrhea—and there were no new safety signals observed. That's actually a good thing, because most oncologists are already comfortable prescribing this drug in general practice. There were dose reductions in 39% of patients, which is a meaningful proportion and suggests that the 200 mg starting dose may be on the higher end for many people—the breast cancer dose in combination with endocrine therapy is 150 mg. So I think there is some work to be done to refine the optimal dosing. That said, even patients who dose-reduced to 150 or 100 mg experienced meaningful clinical benefit, so lower doses should not be seen as a failure.

Pharmacy Times: Patients with dedifferentiated liposarcoma have watched other cancers get transformed by new treatments while their options have barely moved. How does it feel to be presenting this meaningful data in a plenary session at ASCO?

Dickson: It's extremely exciting. This has been a long-term effort—not only for me but also for a remarkable group of collaborators across the country who made it possible. Whenever we can genuinely move the needle for patients in a disease where options have been so limited for so long, it's incredibly rewarding. It's exactly why oncologists go to work every day.