Targeting the PD-1 pathway has changed the therapeutic landscape of several solid tumors and hematologic malignancies. This study, SARC 028, evaluated the safety and efficacy of pembrolizumab in patients with advanced soft-tissue sarcoma (STS) and bone sarcomas.
In this phase 2 study, patients with STS (Arm A) or bone sarcoma (Arm B) received pembrolizumab 200 mg intravenously every 3 weeks. The primary end point was objective response rate (ORR) by RECIST 1.1. The study was also powered to detect an improvement in 3-month progression-free rate.
Arm A enrolled 4 STS subtypes in balanced cohorts: leiomyosarcoma, liposarcoma, undifferentiated pleomorphic sarcoma, and synovial sarcoma. Arm B enrolled osteosarcoma, Ewing sarcoma, and high-grade/dedifferentiated chondrosarcoma (CS).
In Arm A, 7 partial responses were seen (ORR, 17.5%): undifferentiated pleomorphic sarcoma (4 of 10), liposarcoma (2 of 10), leiomyosarcoma (0 of 10), and synovial sarcoma (1 of 10). Median duration of response was 24 weeks. The 3-month progression-free rate was 55%.
In Arm B, the ORR was 5%, reflecting 2 partial responses: 1 of 19 osteosarcomas and 1 of 6 CSs. The toxicity profile of pembrolizumab was consistent with previous published data.
Pembrolizumab showed promising results in patients with undifferentiated pleomorphic sarcoma and liposarcoma. No activity was observed in liposarcoma or Ewing sarcoma.