The SU2C-SARC032 clinical trial revealed that adding the immunotherapy medication pembrolizumab to the standard treatment significantly enhances disease-free survival for patients with advanced soft tissue sarcoma in the limbs.
The SU2C-SARC032 clinical trial revealed that adding the immunotherapy medication pembrolizumab to the standard treatment significantly enhances disease-free survival for patients with advanced soft tissue sarcoma in the limbs.
The results of the study, which were published today in The Lancet, indicate that pembrolizumab could be a new treatment alternative for these patients.
Lead author Yvonne Mowery, M.D., Ph.D., an associate professor of radiation oncology at the University of Pittsburgh and UPMC Hillman Cancer Center, explained, “Soft tissue sarcoma is a rare and intricate disease, consisting of over 50 unique subtypes, making large clinical trials challenging.” She continued, “Progress in treating these patients has stagnated over the years, so it’s incredibly encouraging that our trial demonstrates how pembrolizumab can enhance patient outcomes beyond the existing standard care for those with locally advanced conditions.”
David Kirsch, M.D., Ph.D., the senior author and head of the Radiation Medicine Program at Princess Margaret Cancer Centre in Toronto, Canada, who led the Stand Up To Cancer® (SU2C) Catalyst Research Team behind the trial, added, “This clinical trial represents significant progress for patients with the specific types of sarcoma examined in our study. We discovered that immunotherapy can boost outcomes for patients facing the most aggressive instances of the disease, implying that further refinement of immunotherapy could yield even more significant improvements for our patients.”
Soft tissue sarcoma that occurs in the limbs encompasses various tumors that arise from muscles, tendons, fat, blood vessels, or nerves in the arms and legs. Approximately 50% of patients with large, high-grade sarcomas will eventually develop incurable metastases, making timely intervention crucial before any signs of spread appear, according to Mowery.
“We usually manage patients through a combination of surgery and radiation,” she stated. “Some may also undergo chemotherapy, but its effectiveness varies, and it is quite toxic. This is why we were keen to explore if immunotherapy could potentially enhance outcomes for patients.”
The study involved 20 institutions across the U.S., Canada, Australia, and Italy, enrolling patients diagnosed with stage 3, grade 2 or 3 soft tissue sarcoma in the extremities, including two particular subtypes: undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma.
Patients assigned to the control group received standard treatments, which included preoperative radiation and surgery. In contrast, those in the experimental group received both preoperative and postoperative infusions of pembrolizumab along with standard treatment.
Among 127 participants, the two-year disease-free survival rate was 52% for the control group compared to 67% for the experimental group. This indicates that pembrolizumab usage likely reduces the risk of recurrence or death among these patients.
As anticipated, the occurrence of serious side effects was higher in the experimental group (56%) compared to the control group (31%). However, no treatment-related deaths were reported in either group. Most notably, the findings suggest that pembrolizumab might present a less toxic option than chemotherapy.
While the study’s authors agree it’s premature to conclude whether pembrolizumab enhances overall survival, they plan to keep monitoring the patients to answer this question in the future.
“Our discovery that pembrolizumab substantially improved disease-free survival makes us hopeful that more clinicians will begin integrating immunotherapy into their treatment regimens for these patients,” Mowery expressed. “Given the limited effective treatments for patients with metastatic disease, we aspire to lower the number of patients progressing to metastases, ultimately aiming for better overall survival rates.”
Additional authors of the study can be found in the manuscript.
The SU2C-SARC032 clinical trial was backed by SARC (Sarcoma Alliance for Research Through Collaboration). The initiative received funding from a SU2C Catalyst® grant and was supported by Merck’s (known as MSD outside the U.S. and Canada) Investigator Studies Program, which supplied the study drug and financial assistance. Additional funding came from ANZSA (Australia and New Zealand Sarcoma Association), Cancer Australia, the GPA Andrew Ursini Charitable Fund, and the National Cancer Institute (P30CA046592).
