Dr Roland on a Study of Neoadjuvant Immune-Checkpoint Blockade Across Sarcoma Subtypes

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 a randomized, noncomparative phase 2 study (NCT03307616) of neoadjuvant immune-checkpoint blockade in patients with retroperitoneal dedifferentiated liposarcoma, highlighting outcomes of this investigation.

Within the dedifferentiated liposarcoma arm, approximately 20% of patients exhibited a pathologic complete response (pCR), Roland begins. However, in the undifferentiated pleomorphic sarcoma (UPS) arm, the combination therapy of immunotherapy plus radiation led most patients to demonstrate less than 15% viable tumor mass at the time of surgery, she says. Moreover, the median percent hyalinization within the UPS arm was 89%, indicating minimal residual tumor presence, according to Roland. Historically, pCR rates with radiation therapy alone in patients with UPS have been approximately 30%, Roland notes. Thus, despite the relatively small cohort size, these phase 2 trial findings indicate the efficacy of combining immunotherapy with radiation for patients with UPS, she states.

This study served as a pilot endeavor, delving into these treatment modalities and exploring correlative end points vital to the investigation, Roland notes. Concurrently, the national, phase 2 SU2C-SARC032 trial (NCT03092323) commenced, examining the efficacy of PD-1 inhibitors in combination with radiation vs radiation monotherapy in patients with sarcoma, with disease-free survival as its primary end point, she reports. This larger-scale trial promises insights that complement and expand upon initial findings, and results from this trial are eagerly awaited, Roland explains.

Central to the phase 2 study's significance was its role in elucidating the heterogeneous responses to various immunotherapeutic approachesobserved among different histological subtypes, she continues. Through meticulous biopsy collection at multiple time points, investigators discerned responders from non-responders, Roland says. Acknowledging the inherent variability in treatment response among patients enrolled in clinical trials, the objective was to dissect the underlying differences in tumor characteristics at baseline and in response to immunotherapy, Roland notes. This comprehensive evaluation lays the groundwork for refining future trial designs, she concludes.