Immunotherapy Drug Pembrolizumab Improves Outcomes in Advanced Soft Tissue Sarcoma – 11/12/2024
A groundbreaking clinical trial has shown that adding the immunotherapy drug pembrolizumab to the standard treatment for patients with advanced soft tissue sarcoma of the limb significantly improves disease-free survival. The SU2C-SARC032 trial, led by researchers from the University of Pittsburgh, UPMC, Duke University, and Princess Margaret Cancer Centre, University Health Network, highlights pembrolizumab as a promising new option for patients.
Published in The Lancet, the study addresses the challenges of treating soft tissue sarcoma, a rare and complex disease with over 50 subtypes. “For decades, treatment options for these patients have remained limited. It’s exciting to see that pembrolizumab can improve outcomes beyond the current standard of care for locally advanced disease,” said lead author Dr. Yvonne Mowery, associate professor of radiation oncology at Pitt and UPMC Hillman Cancer Center.
Senior author Dr. David Kirsch, leader of the Stand Up To Cancer® (SU2C) Catalyst Research Team and head of the Radiation Medicine Program at Princess Margaret Cancer Centre, emphasized the significance of the findings. “This trial marks a major advance for patients with aggressive sarcoma. Our results suggest that optimizing immunotherapy further could lead to even greater benefits,” he noted.
Targeting High-Risk Sarcomas
Soft tissue sarcomas of the extremities originate in muscles, tendons, fat, blood vessels, or nerves in the arms and legs. Around half of patients with large, high-grade sarcomas eventually develop incurable metastases, making early intervention critical.
“Current treatment typically involves surgery and radiation, with some patients also receiving chemotherapy,” Mowery explained. “However, chemotherapy is highly toxic and has mixed effectiveness, so we wanted to explore whether immunotherapy could provide better outcomes.”
The study enrolled 127 patients across 20 institutions in the U.S., Canada, Australia, and Italy. Participants had stage 3, grade 2 or 3 soft tissue sarcoma of the extremities, specifically undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma.
Patients in the control group received standard preoperative radiotherapy and surgery, while those in the experimental group also received pembrolizumab infusions before and after surgery. The results were striking:
- Disease-free survival at two years: 67% in the pembrolizumab group vs. 52% in the control group.
- Reduction in recurrence or death: Significantly lower in patients receiving pembrolizumab.
- Toxicity profile: Serious adverse events occurred in 56% of the pembrolizumab group compared to 31% in the control group. However, no treatment-related deaths were reported, and pembrolizumab may be a less toxic alternative to chemotherapy.
While it is too early to determine the impact on overall survival, researchers will continue to follow the patients to gather more data.
Implications for Future Treatment
“Given our findings, we hope more clinicians will incorporate immunotherapy into treatment for these patients,” said Mowery. “With limited options for metastatic sarcoma, reducing the number of patients who develop metastases could ultimately lead to improved survival rates.”
The SU2C-SARC032 trial was sponsored by the Sarcoma Alliance for Research Through Collaboration (SARC) and funded by a SU2C Catalyst® grant. Additional support came from Merck (MSD outside the U.S. and Canada), ANZSA (Australia and New Zealand Sarcoma Association), Cancer Australia, the GPA Andrew Ursini Charitable Fund, and the National Cancer Institute (P30CA046592).
Resource:
https://www.upmc.com/media/news/111224-soft-tissue-sarcoma
