Dr. Roland on Neoadjuvant Checkpoint Blockade in Sarcoma Subtypes

Christina L. Roland, MD, PhD, chief of Sarcoma Surgery; an assistant professor in the Department of Surgical Oncology in the Division of Surgery; and associate medical director of the Sarcoma Center at The University of Texas MD Anderson Cancer Center, discusses the design of a randomized, phase 2 trial with nivolumab (Opdivo) and ipilimumab (Yervoy) in resectable retroperitoneal dedifferentiated liposarcoma, as well as radiation therapy in extremity/truncal undifferentiated pleomorphic sarcoma (UPS).

In the 4-arm study, investigators compared data from the phase 2 SARCO 28 study, which looked at anti–PD-1 alone with a pembrolizumab (Keytruda) monotherapy, and the phase 2 Alliance A091401 study, which demonstrated potentially better efficacy with the combination of anti–CTLA-4 and PD-1, says Roland.

The investigators examined 4 studies examining these 2 agents in the neoadjuvant space to determine which therapy would be more effective in patients with various sarcomas. In patients with extremity/truncal UPS, the standard of care is radiation therapy, but there was also a biologic rationale that checkpoint blockades with radiation could potentially improve efficacy, explains Roland.

Two of the arms included in the study had patients with UPS who had either primary or recurrent disease. Patients who enrolled on the study were then randomized to either nivolumab or ipilimumab plus nivolumab. These patients received 3 doses of therapy before undergoing surgery. The 2 UPS arms were randomized to ipilimumab/nivolumab and received a single dose. Two weeks later, patients started a combination regimen of nivolumab and radiation for 3 doses. After these doses, patients underwent surgery 4-6 weeks following therapy. During that time, data and biopsies were collected, concludes Roland.