A Paradigm Shift for Hard-to-Treat Sarcomas

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Two recent studies by Sylvester Comprehensive Cancer Center researchers are the first to suggest that immunotherapy plays a key role in treating sarcomas, namely angiosarcoma and alveolar soft-part sarcoma.

The findings could change the treatment paradigm for sarcoma types that have few if any treatment options, according to an author on both studies, Jonathan C. Trent, M.D., Ph.D., professor of medicine and director of the sarcoma oncology group at Sylvester, part of the University of Miami Miller School of Medicine.

In a study published May 8 in The Lancet Oncology, Dr. Trent and colleagues conducted a phase 2 trial of 33 advanced sarcoma patients, including 12 with alveolar soft-part sarcoma, treated with the immunotherapy pembrolizumab and targeted therapy axitnib.

Sylvester researchers are the first in the world to study the drug combination in alveolar soft-part sarcoma — a cancer type that has no known effective chemotherapy options, according to Dr. Trent.

“We found at three months that 25 percent of patients overall had substantial regression of their tumors, and in another 28 percent of patients, their tumors quit growing. So more than half, 53 percent, of patients achieved benefit from the immunotherapy combined with targeted therapy treatment,” Dr. Trent said. “Fifty-five percent of alveolar soft-part sarcoma patients had substantial reduction in their tumor size. Another 20 percent had stability of their tumors.”

There were no treatment-related deaths and treatment was well tolerated overall with manageable toxicity, according to the authors.

“The gold standard treatment now is this combination. It seems to be the most effective treatment out there for alveolar soft-part sarcoma,” Dr. Trent said.

In a paper published August 8 in the Journal for ImmunoTherapy in Cancer, Dr. Trent and colleagues used the combination therapy to treat another highly aggressive, rare malignancy: angiosarcoma.

They found tumors regressed in 71 percent of those patients, with only 29 percent experiencing tumor growth at three months.

“What’s important about the angiosarcoma study is these are patients that were resistant to chemotherapy, so they had exhausted all chemotherapy options,” Dr. Trent said.

Angiosarcoma starts as localized disease but is highly infiltrative, making treatment of the disease in its early stages challenging.

“Systemic chemotherapy is used in the metastatic setting and in patients with high-risk localized disease in neoadjuvant or adjuvant settings,” the researchers wrote. “However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patients with angiosarcoma.”

Targeted immunotherapy could be a new option for treating angiosarcoma, according to the study.

This new wave in sarcoma treatment came as a surprise to some, according to Dr. Trent.

“Historically sarcoma has been thought of as a disease in which immunotherapy had no role, but we found that if you look at select types, there may be benefit,” he said.

Sylvester Comprehensive Cancer Center is expected to lead a phase 3 trial, seeking FDA approval and looking at treating sarcoma patients with the same combination therapy. Researchers have not yet started recruiting patients for that study, according to Dr. Trent.


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