A phase II trial (SU2C-SARC032) has demonstrated that the addition of perioperative pembrolizumab to preoperative radiation therapy and surgery significantly improves disease-free survival in patients with stage III soft-tissue sarcoma of the extremity. The findings, published in The Lancet, suggest a promising new treatment option for this patient population.
The open-label trial, conducted across multiple sites in Australia, Canada, Italy, and the United States, enrolled 127 patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle between November 2017 and November 2023. Patients were randomized to receive preoperative external-beam radiotherapy (50 Gy in 25 daily fractions) followed by surgery with (n = 64) or without (n = 63) pembrolizumab. Pembrolizumab was administered at 200 mg every 3 weeks for 3 neoadjuvant cycles (before, during, and after radiotherapy) and up to 14 adjuvant cycles. The primary endpoint was disease-free survival.
Improved Disease-Free Survival
After a median follow-up of 43 months, the study revealed a significant improvement in disease-free survival at 2 years in the pembrolizumab group (67%, 90% CI = 58%–78%) compared to the control group (52%, 90% CI = 42%–64%). The hazard ratio (HR) was 0.61 (90% CI = 0.39–0.96, P = .035). Distant disease–free survival at 2 years was also improved, at 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).
Adverse Events
The addition of pembrolizumab was associated with a higher incidence of grade ≥ 3 adverse events, occurring in 56% of the pembrolizumab group compared to 31% of the control group. The most common adverse events in the pembrolizumab group were anemia (10%), wound infection (10%), and hypertension (9%), while wound infection (9%) and wound dehiscence (6%) were more frequent in the control group. Notably, no treatment-related deaths were observed.
Expert Commentary
The investigators concluded that the 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. According to the authors, this 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, served as the corresponding author for The Lancet article.
