Christina L. Roland, MD, MS, FACS, chief of Sarcoma Surgery and an assistant professor in the Department of Surgical Oncology in the Division of Surgery, as well as the associate medical director of the Sarcoma Center at The University of Texas MD Anderson Cancer Center, discusses the results from a phase 2 study (NCT03307616) evaluating neoadjuvant checkpoint blockade study in patients with undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS).

Twenty-three patients were determined to be evaluable and data for them were reported in a presentation delivered atthe 

; 4 additional patients have been treated but they did not have sufficient data to report at the time of the presentation, explains Roland. A total of 14 patients had DDLPS and 9 patients had UPS were then randomized. The most exciting findings are in the UPS arm, according to Roland.

In patients with UPS, no difference between nivolumab (Opdivo) and nivolumab plus ipilimumab (Yervoy), except more toxicity was reported in the doublet arm, Roland adds. In terms of efficacy, the majority of patients had less than 15% of residual viable tumor on their surgical specimen. Historical data were examined before the study was designed to determine whether there was a median for either radiation or chemoradiation alone. The median for the amount of hyalinization for radiation was 5% to 10%. In the study presented at the ASCO Annual Meeting, the median was 93% in patients with UPS. Although a radiation-alone group was not included in the trial, by using historical cohorts, it may be deduced that the amount of hyalinization in patients with UPS is better than what has been seen previously, concludes Roland.

Videos

Christina L. Roland, MD, MS, FACS, discusses the results from a phase 2 study evaluating neoadjuvant checkpoint blockade study in patients with undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

Dr. Roland on Findings From a Phase 2 Study With Neoadjuvant Checkpoint Blockade in Sarcoma

Christina L. Roland, MD, MS, FACS, chief of Sarcoma Surgery and 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 safety profile of neoadjuvant checkpoint blockade in patients with undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS).

In the study, investigators examined neoadjuvant nivolumab (Opdivo) monotherapy and the combination of ipilimumab (Yervoy) plus nivolumab with and without radiation in patients with treatment-naïve or locally recurrent DDLPS and UPS.

In general, patients tolerated the regimen relatively well, says Roland. In the DDLPS group that just received nivolumab,essentially no grade 3 toxicities were reported. In all other groups, the most common toxicity reported was colitis, which was not surprising in the groups that received ipilimumab, says Roland. Even in the nivolumab/radiation group, however, it seemed that adding radiation increased toxicity, which was more equivalent to dual checkpoint blockade, explains Roland. Patients in the triplet group experienced the most toxicity.

All patients were able to recover from their toxicity and only 1 surgical delay was reported in the ipilimumab/nivolumab arm because of this, although that patient was later able to undergo surgery. In the 3 arms that did not receive nivolumab, at least 30% of patients were unable to complete the treatment because of toxicity, according to Roland.

Notably, even in patients with UPS who received either nivolumab plus radiation or ipilimumab/nivolumab plus radiation, 40% and 50%, respectively, did not receive all of the therapy but still had a significant response. More correlative analyses need to be done, but it is possible that these patients do not need the 4 total doses and 1 or 2 doses might still be enough to experience a response, concludes Roland.

Christina L. Roland, MD, MS, FACS, discusses the safety profile of neoadjuvant checkpoint blockade in patients with undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

Dr. Roland on the Safety of Neoadjuvant Checkpoint Blockade in Sarcoma

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 rationale for a phase 2 study (NCT03307616) evaluating neoadjuvant checkpoint blockade study in patients with undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS).

In recent years, immunotherapy has started to emerge as a potential treatment modality in sarcoma, says Roland. At the 2019 ASCO Annual Meeting, results of the phase 2 SARC028 trial demonstrated objective responses with pembrolizumab (Keytruda) rates in both UPS and DDLPS.

In another phase 2 trial, nivolumab (Opdivo) was evaluated as a single-agent and in combination with ipilimumab (Yervoy) in the neoadjuvant setting. Notably, in this setting, patients typically have a lower burden of disease and are more likely to be cured.

The randomized phase 2 trial was modeled after a melanoma study, says Roland. The study was designed to assess the pathological response, a surrogate outcome for survival.

The results of the study showed significant clinical activity in patients with UPS who received nivolumab with or without ipilimumab plus concurrent radiation therapy, Roland concludes.

Christina L. Roland, MD, PhD, discusses the rationale for a phase 2 study evaluating neoadjuvant checkpoint blockade study in patients with undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

Dr. Roland on the Rationale for a Neoadjuvant Checkpoint Blockade in Sarcoma 

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.

Christina L. Roland, MD, PhD, discusses the design of a randomized, phase 2 trial with nivolumab and ipilimumab in resectable retroperitoneal dedifferentiated liposarcoma, as well as radiation therapy in extremity/truncal undifferentiated pleomorphic sarcoma.

Christina L. Roland, MD, PhD

Articles

Dr. Roland on Findings From a Phase 2 Study With Neoadjuvant Checkpoint Blockade in Sarcoma

Dr. Roland on the Safety of Neoadjuvant Checkpoint Blockade in Sarcoma

Dr. Roland on the Rationale for a Neoadjuvant Checkpoint Blockade in Sarcoma

Dr. Roland on Neoadjuvant Checkpoint Blockade in Sarcoma Subtypes