Investigators Observe Differences in Toxicity for Sarcoma Due to Dosing

July 14, 2020

Gary K. Schwartz, MD, discusses adverse events seen in patients with metastatic sarcoma participating in the Alliance A091401 trial.

Gary K. Schwartz, MD, professor of medicine, chief of the Division of Hematology/Oncology, ​and deputy director at the Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, discusses adverse events (AEs) seen in patients with metastatic sarcoma participating in the Alliance A091401 trial (NCT02500797).

According to Schwartz, before this study there were relatively low rates of treatment-related AEs in this setting of 10% to 15%. The design of Alliance A091401, which investigated nivolumab (Opdivo) and ipilimumab (Yervoy) in patients with gastrointestinal stromal tumor, undifferentiated pleomorphic sarcoma (UPS), and dedifferentiated liposarcoma (DDLS), used a lower dose of ipilimumab. The standard dose for melanoma is 3 mg/kg of ipilimumab and 1 mg/kg of nivolumab. This study did the opposite, with 1 mg/kg of ipilimumab and 3 mg/kg of nivolumab.

The reduction of dosing with ipilimumab reduced immune-related AEs in the DDLS and UPS groups. Schwartz says this outcome shows this regimen is a much safer approach for patients with sarcoma; he says AEs in this patient population are always a problem because physicians have to decide if the value of ipilimumab merits the increased immune-related toxicities.

In patients with melanoma, those concerns remain, and trials looking into it now are showing that any dose of ipilimumab does not make a difference, Schwartz says. This study, however, demonstrated reduced toxicity with the lower dose of ipilimumab and improved benefit in response rate.

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