Pembrolizumab May Be Beneficial in a Subset of Soft-Tissue Sarcomas

Treatment options are limited for patients with advanced sarcomas. Immune checkpoint blockade therapies, including the anti–PD-1 antibody pembrolizumab, have had success in a number of tumor types, but have not been well studied for the treatment of sarcoma. In the SARC028, two-cohort, open-label, phase II trial, Tawbi and colleagues evaluated the safety and efficacy of pembrolizumab in patients with advanced soft-tissue or bone sarcoma. A total of 84 patients were enrolled and treated with pembrolizumab. The primary endpoint was objective response rate. Secondary endpoints included incidence of adverse events, progression-free survival, and overall survival. There were 40 evaluable patients in each cohort. Overall, 7 of 40 (18%) patients with soft-tissue sarcoma had an objective response, including 4 of 10 (40%) patients with undifferentiated pleomorphic sarcoma, 2 of 10 (20%) patients with liposarcoma, and 1 of 10 (10%) patients with synovial sarcoma. None of the 10 patients with leiomyosarcoma achieved an objective response. The median progression-free survival for patients with soft-tissue sarcoma was 18 weeks, the 12-week progression-free survival 55%, the median overall survival was 49 weeks, and the median duration of response was 33 weeks. Of the 40 patients with bone sarcoma, 2 (5%) had an objective response, 1 of 22 patients (5%) with osteosarcoma and 1 of 5 patients (20%) with chondrosarcoma. None of the 13 patients with Ewing sarcoma experienced an objective response. The median progression-free survival was 8 weeks, median overall survival was 52 weeks, and median duration of response was 43 weeks. The safety profile was consistent with what had previously been reported for pembrolizumab. Collectively, the results of the SARC028 trial suggest that immune checkpoint blockade may be effective in a subset of patients with soft-tissue sarcoma, and further clinical studies are ongoing in patients with undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicenter, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 2017;18:1493–501.

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