Dr. Schwartz on the Benefit of Dose Reduced Nivolumab/Ipilimumab in Metastatic Sarcomas

Gary K. Schwartz, MD, a professor of medicine, chief of the Division of Hematology​/Oncology, and deputy director of Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, discusses the benefit of dose reducing ipilimumab (Yervoy) plus nivolumab (Opdivo) in metastatic sarcomas.

Although there was no increase in responses in the ALLIANCE A091401 trial, there was a suggestion of improvement in overall survival (OS) and progression-free survival (PFS). This indicates that some patients with gastrointestinal stromal tumor experienced stabilization of disease that was not reflected by RECIST criteria, says Schwartz. There are subtypes of sarcomas that are sensitive to immunotherapy, such as dedifferentiated liposarcoma (DDLS) and undifferentiated pleomorphic (UPS) sarcoma, though the numbers are low. For example, in a SARC study, investigators gave single-agent pembrolizumab (Keytruda) to patients with sarcoma and did not see an overwhelming number of responses, adds Schwartz.

It has been suggested that the combination of ipilimumab plus nivolumab is superior to nivolumab alone. Before this study, relatively low treatment-related adverse effects (AEs) had been observed with the regimen, explains Schwartz. The study design used a lower dose of ipilimumab, also known as the “sarcoma dosing,” with patients being given a full dose of nivolumab at 3 mg/kg and 1 mg/kg of ipilimumab. With that dose reduction of ipilimumab, a drop in immune-related AEs was observed in the DDLS and UPS subgroups, providing a safer option for patients.

These results weigh ipilimumab's benefit against its risk of increased immune-related toxicities. In melanoma, this remains a concern because studies now suggest that it does not matter what dose of ipilimumab is used. However, inthe ALLIANCE A091401 study's lower dose of ipilimumab yielded a reduced toxicity, while still suggesting an improved benefit with regard to response rate, OS, and PFS, concludes Schwartz.