Pembrolizumab Shows Promise in Two Soft-Tissue Sarcoma Subtypes

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A phase II study found that the immunotherapy agent pembrolizumab has meaningful clinical activity in patients with two subtypes of advanced sarcoma.

The phase II SARC028 study found that the immunotherapy agent pembrolizumab has meaningful clinical activity in patients with two subtypes of advanced sarcoma. This included undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma, while other subtypes including Ewing sarcoma and leiomyosarcoma did not respond to the therapy.

A different type of immune therapy, mifamurtide, has been shown to be effective in osteosarcoma. “However, except for mifamurtide, immunotherapy has had little therapeutic benefit in patients with soft-tissue sarcoma or bone sarcoma, with studies using cytokines or immune adjuvants not achieving their primary endpoints,” wrote study authors led by Hussein A. Tawbi, MD, of the University of Texas MD Anderson Cancer Center in Houston.

The study looked at immune checkpoint inhibition with pembrolizumab in the advanced sarcoma setting. It included 86 patients, 80 of whom were available for analysis, divided into 2 cohorts of 40 bone sarcoma patients and 40 soft-tissue sarcoma patients; the results were published in Lancet Oncology.

The bone sarcoma patients had a median age of 33 years, while the soft-tissue sarcoma patients had a median age of 53 years. Just over 60% of both cohorts were men, and most patients in both cohorts had received at least two prior therapies.

Responses were infrequent in the bone sarcoma patients. Two patients in that cohort had a partial response (5%): one who had chondrosarcoma and one who had osteosarcoma. There were no responses among the 13 patients with Ewing sarcoma. Another 9 bone sarcoma patients (23%) had stable disease, and 29 (93%) had progressive disease.

In the soft-tissue sarcoma group, there was one complete response (3%) and six partial responses (15%), for an overall response rate of 18%. Three of 10 patients with undifferentiated pleomorphic sarcoma (30%) had a partial response, and this group also contained the one complete response. Two liposarcoma patients (20%) had a partial response, as did one synovial sarcoma patient (10%). Another 15 soft-tissue sarcoma patients (38%) had stable disease, and 18 patients (45%) had progressive disease.

Among the most frequent grade 3 or higher adverse events were anemia (14%), decreased lymphocyte count (12%), prolonged activated partial thromboplastin time (10%), and others.

“If the clinical activity of pembrolizumab can be confirmed in other, larger studies, our findings could change practice given that undifferentiated pleomorphic sarcoma and liposarcoma are two of the three most common soft-tissue sarcomas,” the authors concluded. Together, those two subtypes represent more than 30% of all soft-tissue sarcomas.

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