Immunotherapy for Advanced Soft-Tissue and Bone Sarcoma
The phase II SARC028 trial has shown activity of pembrolizumab (Keytruda) in some subtypes of advanced sarcoma. These findings were reported by Tawbi et al in The Lancet Oncology.
Study Details
In the study, 84 patients with advanced soft-tissue sarcoma aged ≥ 18 years (n = 42) or bone sarcoma aged ≥ 12 years (n = 42) were enrolled from 12 U.S. academic centers in the Sarcoma Alliance for Research through Collaboration (SARC) between March 2015 and February 2016 and were treated with pembrolizumab at 200 mg every 3 weeks. Patients had metastatic or unresectable locally advanced disease, had received up to three previous lines of systemic anticancer therapy, and had at least one measurable lesion on Response Evaluation Criteria in Solid Tumors v1.1. The primary endpoint was investigator-assessed objective response.
Response Rates
Median follow-up was 17.8 months. Response was observed in 7 of 40 evaluable patients (18%) with soft-tissue sarcoma, including 4 of 10 (40%) with undifferentiated pleomorphic sarcoma, 2 of 10 (20%) with liposarcoma, 1 of 10 (10%) with synovial sarcoma, and 0 of 10 with leiomyosarcoma. Response was observed in 2 of 40 (5%) evaluable patients with bone sarcoma, including 1 of 22 (5%) with osteosarcoma and 1 of 5 (20%) with chondrosarcoma; no responses were observed in 13 patients with Ewing’s sarcoma.
Adverse Events
The most common grade ≥ 3 adverse events were anemia (14%), decreased lymphocyte count (12%), prolonged activated partial thromboplastin time (10%), and decreased platelet count (7%) in the bone sarcoma group and anemia (7%), decreased lymphocyte count (7%), and prolonged activated partial thromboplastin time (7%) in the soft-tissue sarcoma group. Serious adverse events occurred in 11% of patients, including 12% of the bone sarcoma group and 10% of the soft-tissue sarcoma group; five of these patients had serious immune-related adverse events, including two with adrenal insufficiency, two with pneumonitis, and one with nephritis.
The investigators concluded: “Pembrolizumab has meaningful clinical activity in patients with undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma. Enrolment to expanded cohorts of those subtypes is ongoing to confirm and characterise the activity of pembrolizumab.”
The study was funded by Merck, SARC, Sarcoma Foundation of America, Quad W Foundation, Pittsburgh Cure Sarcoma, and Ewan McGregor.
Hussein A. Tawbi, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of The Lancet Oncology article.
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