Dr. Schwartz on the Updated Design of the Alliance A091401 Trial in Metastatic Sarcomas

Gary K. Schwartz, MD, professor of medicine; chief, Division of Hematology​/Oncology; and ​deputy director of the Columbia University Herbert Irving Comprehensive Cancer Center, discusses the updated design of the phase 2 Alliance A091401 trial for metastatic sarcomas.

The Alliance A091401 trial is a phase 2 randomized study comparing nivolumab (Opdivo) alone versus nivolumab plus ipilimumab (Yervoy) in patients with advanced sarcomas. The original paper showed that the combination of nivolumab plus ipilimumab resulted in higher response rates than nivolumab alone, says Schwartz.

In the original study design, it appeared that there were several subtypes of sarcoma—particularly undifferentiated pleomorphic sarcoma (UPS) and liposarcoma—in which an increased response rate relative to other subtypes was observed.

In the original study design, no particular sarcoma subtype was included because, at that time, no data indicated that one subtype would have a superior outcome with the treatment over another. As such, patients with all subtypes of sarcoma were included; this is complicated because sarcoma is a disease with numerous different subtypes, all of which are biologically different and have different outcomes, explains Schwartz.

When the study was originally conducted in 2017, investigators were curious to know whether 1 subtype would have a superior outcome over another with the approach. Data from the first study published in 2018 in the Lancet Oncology suggested that UPS and dedifferentiated liposarcoma subtypes would both fare better with the combination, concludes Schwartz.