Dr Roland on the Utility of Neoadjuvant Immune-Checkpoint Blockade in Liposarcoma

Christina L. Roland, MD, MS, FACS, associate professor, surgery, section chief, Sarcoma Surgery, vice chair, Research, Department of Surgical Oncology, associate medical director, Sarcoma Center, The University of Texas MD Anderson Cancer Center; executive director, surgery, MD Anderson Cancer Network, discusses the rationale for and design of a randomized, noncomparative phase 2 study (NCT03307616) of neoadjuvant immune-checkpoint blockade in patients with retroperitoneal dedifferentiated liposarcoma.

The main objective of the study was to assess whether incorporating immunotherapy with surgery would enhance the pathologic response rates in this patient population, Roland begins. Historically, data from various institutions have shown pathologic response rates ranging from 10% to 30% with chemotherapy or radiation in patients with liposarcoma, she says. Thus, the study investigated whether administering 3 or 4 doses of immunotherapy prior to surgery, in combination with radiation therapy, would lead to increased pathologic responses upon tumor removal in this patient population, Roland explains.

The study was structured with 2 distinct cohorts, 1 of which consisted of patients with retroperitoneal differentiated liposarcoma eligible for surgery, who received either 3 doses of nivolumab (Opdivo) or a combination of ipilimumab (Yervoy) and nivolumab, followed by random assignment into 1 of these 2 treatment arms before undergoing surgery, she explains.

The second cohort involved patients with undifferentiated pleomorphic sarcoma of the extremity or trunk, traditionally treated with preoperative radiation therapy, she adds. These patients were randomly assigned to receive either 1 dose of nivolumab followed by nivolumab plus radiation or combination ipilimumab and nivolumab followed by combination nivolumab and radiation prior to undergoing surgery, Roland elucidates. The primary end point for both cohorts was pathologic response, assessed by percent hyalinization at the time of surgical resection, she reports.

Due to the existing data on non-immunotherapy treatments, significant pathologic responses were not expected, in this trial, she says. Therefore, the end point of percent hyalinization was chosen, as it had previously been shown to correlate with overall survival, thus guiding the study design, Roland concludes.