Addition of pembrolizumab to the standard treatment regimen significantly improves disease-free survival in patients with advanced soft tissue sarcoma of the limb, according to the SU2C-SARC032 clinical trial. The study, led by researchers from the University of Pittsburgh, UPMC, Duke University, and Princess Margaret Cancer Centre, was published in The Lancet and establishes pembrolizumab as a new treatment option for this disease.
Dr. Yvonne Mowery, lead author and associate professor of radiation oncology at Pitt and UPMC Hillman Cancer Center, noted the challenges in treating soft tissue sarcoma due to its rarity and complexity, with over 50 different subtypes. "Since we haven’t made much progress in treating these patients for decades, it’s really exciting that this trial shows pembrolizumab can improve outcomes beyond current standard of care for patients with locally advanced disease."
Study Details and Findings
The multi-institutional study enrolled patients with stage 3, grade 2 or 3 soft tissue sarcoma of the extremities, specifically undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma. Patients were treated across 20 institutions in the U.S., Canada, Australia and Italy.
The control group received standard of care, including preoperative radiotherapy and surgery. The experimental group received both preoperative and postoperative infusions of pembrolizumab in addition to standard of care.
The two-year disease-free survival rate was 67% in the pembrolizumab group compared to 52% in the control group, demonstrating a significant reduction in recurrence or death. While serious adverse events were more frequent in the experimental group (56%) compared to the control group (31%), no treatment-related deaths occurred in either group.
Implications for Treatment
Dr. David Kirsch, senior author and leader of the Stand Up To Cancer® (SU2C) Catalyst Research Team, highlighted the significance of the findings. "This clinical trial is a major advance for patients with the kinds of sarcoma that were included in our study. We found that immunotherapy can improve outcomes for patients with the most aggressive form of the disease, suggesting that further optimization of immunotherapy may lead to even greater gains for our patients."
Soft tissue sarcoma of the extremity is a group of tumors that originate in the muscles, tendons, fat, blood vessels or nerves of the legs and arms. Approximately half of patients with large, high-grade sarcomas develop incurable metastases, making early intervention critical.
Future Directions
Researchers will continue to monitor patients to assess the impact of pembrolizumab on overall survival. Dr. Mowery expressed hope that the improved disease-free survival will lead to broader adoption of immunotherapy in clinical practice. "Based on our finding that pembrolizumab significantly improved disease-free survival, we hope that more clinicians will start incorporating immunotherapy into their practice for these patients. Given that there are such limited effective options for patients with metastatic disease, our hope is that reducing the number of patients who develop metastases will ultimately lead to improvements in overall survival."
The SU2C-SARC032 clinical trial was sponsored by SARC (Sarcoma Alliance for Research Through Collaboration) and funded by a SU2C Catalyst® grant, with support from Merck’s Investigator Studies Program.
