Dr Mowery on Pembrolizumab Plus Radiation Therapy and Surgery in Soft Tissue Sarcoma

“We did see a statistically significant improvement in DFS in the experimental arm that included pembrolizumab.”

Yvonne Mowery, MD, PhD, associate professor, Department of Radiation Oncology, UPMC Hillman Cancer Center/University of Pittsburgh, radiation oncologist, Mary Hillman Jennings Radiation Oncology, UPMC Shadyside, discusses findings from the phase 2 SU2C-SARC032 trial (NCT03092323) investigating perioperative pembrolizumab (Keytruda) in combination with standard-of-care (SOC) radiotherapy followed by surgery vs radiotherapy and surgery alone in patients with soft tissue sarcoma.

This trial demonstrated significant improvements in disease-free survival (DFS) with the addition of pembrolizumab to SOC, Mowery begins. The 2-year DFS rate, which served as the trial’s primary end point, was 67% (90% CI, 58%-78%) in the pembrolizumab arm (n = 64) vs 52% (90% CI, 42%-64%) in the SOC alone arm (n = 63), translating to an absolute improvement of 15% (HR, 0.61; 90% CI, 0.39-0.96).

Following the presentation of early findings from this trial at the 2024 ASCO Annual Meeting, many oncologists began integrating pembrolizumab into their clinical practice for the treatment of patients with soft tissue sarcoma, including in settings where chemotherapy is less commonly used, Mowery says. In the trial, the greatest benefit with the addition of pembrolizumab to SOC was observed in patients with grade 3 undifferentiated pleomorphic sarcoma or dedifferentiated pleomorphic liposarcoma, she notes. Many patients with these high-risk subtypes now receive perioperative pembrolizumab as part of their treatment plan, she explains.

Future directions for optimizing the management of soft tissue sarcoma include exploring the integration of immunotherapy with chemotherapy, according to Mowery. Although chemotherapy’s potential immunosuppressive effects could theoretically counteract the efficacy of immunotherapy, certain chemotherapeutic agents used in soft tissue sarcoma have been shown to induce immunogenic cell death, which could result in a cooperative or synergistic effect between these 2 classes of agents, she adds. However, this hypothesis requires experimental validation, as the SU2C-SARC032 trial did not evaluate the use of pembrolizumab plus chemotherapy, she cautions.

Another area of interest for research in soft tissue sarcoma involves dual immune checkpoint blockade, Mowery emphasizes. Pembrolizumab targets PD-1, and early studies have explored combining anti-PD-1 therapy with anti-CTLA-4 therapy, she reports. This combination has shown promise in other malignancies and is being considered for future randomized trials in soft tissue sarcoma, she concludes.