Clinical trial shows immunotherapy drug pembrolizumab improves outcomes for patients with soft tissue sarcoma

Addition of the immunotherapy drug pembrolizumab to standard of care for patients with advanced soft tissue sarcoma of the limb significantly improved disease-free survival, according to the results of the SU2C-SARC032 clinical trial led by researchers from the University of Pittsburgh, UPMC, Duke University and Princess Margaret Cancer Center, University Health Network.

The findings, published in The Lancet, establish pembrolizumab as a new option for patients with this disease.

“Soft tissue sarcoma is a rare and complex disease with over 50 different subtypes, which makes it hard to study in large clinical trials,” said lead author Yvonne Mowery, M.D., Ph.D., associate professor of radiation oncology at Pitt and UPMC Hillman Cancer Center.

“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.”

Senior author David Kirsch, M.D., Ph.D., leader of the Stand Up To Cancer (SU2C) Catalyst Research Team, which ran the clinical trial, and head of the Radiation Medicine Program at Princess Margaret Cancer Center at the University Health Network in Toronto, Canada, added, “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. About half of patients with large, high-grade sarcomas develop incurable metastases, so intervention before signs of metastatic disease is essential, according to Mowery.

“We typically treat patients with a combination of surgery and radiation therapy,” she said. “Some patients also receive chemotherapy, but the data are mixed on its effectiveness and it’s also very toxic, so we were interested in seeing whether immunotherapy could improve outcomes for patients.”

Across 20 institutions in the U.S., Canada, Australia and Italy, the researchers enrolled patients with stage 3, grade 2 or 3 soft tissue sarcoma of the extremities, including two subtypes—undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma.

Patients in the control group received standard of care, which included preoperative radiotherapy and surgery, while those in the experimental group received both preoperative and postoperative infusions of pembrolizumab, in addition to standard of care.

In a total of 127 patients, the two-year disease-free survival rate was 52% for the control group and 67% for the experimental group, indicating that the addition of pembrolizumab reduced recurrence or death for patients.

As expected, serious adverse events were more frequent in the experimental group (56%) compared with the control group (31%), but there were no deaths related to treatment in either group. Importantly, these findings suggest that pembrolizumab may be a less toxic treatment option than chemotherapy.

While the researchers say it’s too early to say whether the addition of pembrolizumab improves overall survival, they will continue to monitor these patients to help answer that question.

“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,” said Mowery.

“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.”