First Positive Phase 3 Trial in a Rare, Aggressive Sarcoma  

By Dr. Gary Schwartz, Alliance for Rare Cancers Vice Chair of the Board and  Director of the Case Comprehensive Cancer Center | Photo courtesy of Cleveland Clinic 

For patients with dedifferentiated liposarcoma — a rare, aggressive soft tissue cancer with very few effective treatment options — ASCO 2026 brought a historic milestone.

Of the Top 5 Takeaways at ASCO, the phase 3 SARC041 trial, the first-ever positive phase 3 trial in this disease, presented by Mark Dickson, MD found that Verzenio (abemaciclib), a cyclin dependent kinase 4 (CDK4) inhibitor, significantly slowed disease progression compared with placebo, representing a 62% reduction in the risk of progression or death.

This drug, which is widely approved for certain breast cancers, will now become the first-line therapy for this rare disease; it has changed the standard of care.

20 years ago, I co-authored the first paper reporting on CDK4 expression in liposarcoma showing that multiple copies of this gene are expressed in liposacoma cells (a process called gene amplification). This makes it an oncogenic driver for cancer growth. We studied another CDK inhibitor Ibrance (palbociclib) that can effectively inhibit liposarcoma cells from growing. Based on this, we ran a phase 2 clinical study at Memorial Sloan Kettering Cancer Center (MSKCC) with Ibrance in patients with this rare cancer.

 Although this study found the drug to have a positive effect in delaying tumor growth, it was also found to be effective in breast cancer, effectively turning research funding away from the rare cancer to the more common cancer. It took over a decade for this other CDK4 inhibitor (abemaciclib) to undergo the definitive randomized phase 3 clinical trial that has led to its recognition as the new standard of care in this disease.

ASCO presenter Mark Dickson, now a full associate professor at MSKCC, was my Fellow at MSKCC over a decade ago when he and I co-authored the first clinical trial on Ibrance in this disease. For this work, he was awarded both the Conquer Cancer Young Investigator Award and the Career Development Award from the American Society of Clinical Oncology (ASCO). It was these exciting results in liposarcoma that maintained the early interest in this class of drugs, long before it became known as a breast cancer drug.

Research funding for rare cancer is a major unmet need. Finally, we now have a rare cancer study proving what our basic and translational research showed over a decade ago: that the targeting of CDK4 is a safe and effective treatment in this rare disease.

Dr. Gary Schwartz is Vice Chair of the Alliance for Rare Cancers Board of Directors. ARC is a fiscally sponsored program of the Jedi Rare Cancer Foundation. Governed by respected leaders across the rare cancer innovation system, ARC provides a venue for rare cancer stakeholders to co-create and implement large-scale collaborative partnerships across multiple rare tumor types to accelerate cures for all rare cancers.