Study Assesses Response to Pembrolizumab Based on Biomarkers in Patients With Soft Tissue or Bone Sarcomas

Of the 86 patients enrolled, 80 were evaluable at data cutoff. Forty patients with soft tissue sarcoma had undifferentiated pleomorphic sarcoma (UPS; n = 10), dedifferentiated liposarcoma (DDLPS; n = 10), synovial sarcoma (SS; n = 10), and leiomyosarcoma (n = 10), whereas the 40 patients with bone sarcoma had osteosarcoma (OS), Ewing sarcoma, or dedifferentiated chondrosarcoma (CS).

After a median follow-up of 14.5 months among those with soft tissue sarcoma, the objective response rate (primary endpoint) was 18% and 12-week progression-free survival was 55% (95% CI = 42−71). Clinical activity varied by histologic subtype, with one complete response and three partial response in those with UPS (40% overall response rate), two partial responses in those with DDLPS, and one partial response in those with SS.

After a median follow-up of 12.3 months for those with bone sarcoma, the overall response rate was 5% and 12-week PFS was 28% (95% CI = 14−41), with one partial response in those with OS and one partial response in those with CS.

Biopsies were extracted prior to treatment with pembrolizumab and during therapy in 70 patients. Three patients (4%) were PD-L1-positive, all of which had UPS. Of the two evaluable patients, one had a complete response and one had a partial response. All PD-L1-positive samples had CD8+ T-cell infiltration. After treatment with pembrolizumab, there were no PD-L1-positive samples.

“Pembrolizumab has clinical activity in UPS and LPS, and expansion cohorts in those subtypes are planned,” the authors concluded. “Pre-treatment PD-L1 expression was infrequent, but correlated with T-cell infiltration and response in UPS and OS.”

Ongoing analyses include circulating cytokine and checkpoint levels and exome, transcriptome, and T-cell receptor sequencing.