In a phase II trial (SU2C-SARC032) reported in The Lancet, Mowery et al found that the addition of perioperative pembrolizumab to preoperative radiation therapy and surgery improved disease-free survival in patients with stage III soft-tissue sarcoma of the extremity.
Study Details
In the open-label trial, 127 patients (modified intention-to-treat population) with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle were enrolled from sites in Australia, Canada, Italy, and the United States between November 2017 and November 2023. Patients were randomly assigned to receive preoperative external-beam radiotherapy at 50 Gy in 25 daily fractions followed by surgery with (n = 64) or without (n = 63) pembrolizumab. Pembrolizumab was given at 200 mg every 3 weeks in 3 neoadjuvant cycles (before, during, and after radiotherapy) and for up to 14 adjuvant cycles. The primary endpoint was disease-free survival.
Key Findings
Median follow-up was 43 months. Disease-free survival at 2 years was 67% (90% confidence interval [CI] = 58%–78%) in the pembrolizumab group vs 52% (90% CI = 42%–64%) in the control group (hazard ratio [HR] = 0·61, 90% CI = 0.39–0.96, P = .035). Distant disease–free survival at 2 years was 67% vs 52% (HR = 0.62, 95% CI = 0.36–1.07, P = .085). Overall survival at 2 years was 88% vs 85% (HR = 0.67, 95% CI = 0.33–1.39, P = .28).
Grade ≥ 3 adverse events occurred in 56% of the pembrolizumab group vs 31% of the control group. The most common events were anemia (10%), wound infection (10%), and hypertension (9%) in the pembrolizumab group and wound infection (9%) and wound dehiscence (6%) in the control group. No treatment-related deaths were observed.
The investigators concluded: “Addition of pembrolizumab to preoperative radiotherapy and surgery improves disease-free survival for patients with stage III undifferentiated pleomorphic sarcoma and pleomorphic or dedifferentiated liposarcoma of the extremity, which establishes a promising new treatment option for these patients.”
David G. Kirsch, MD, of the Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, is the corresponding author of The Lancet article.
Disclosure: The study was supported by Stand Up To Cancer and Merck Sharp & Dohme. For full disclosures of the study authors, visit thelancet.com.
