Cabozantinib Shows Early Promise in Soft-Tissue Sarcoma

The first phase II study of cabozantinib in soft-tissue sarcoma yielded several responses, including several subtypes such as alveolar soft-part sarcoma (ASPS) and myxoid liposarcoma.

VEFG levels are elevated in some patients with soft-tissue sarcoma, and some sarcoma cell lines also express high levels of activated c-Met receptor. “We hypothesized that if we could inhibit both the c-Met as well as VEGF, we would see some activity,” said Alice Chen, MD, of the National Cancer Institute in Bethesda, Maryland. She presented results of the study of cabozantinib, a multikinase inhibitor of MET, VEGFR2, and other targets, at the Connective Tissue Oncology Society (CTOS) 2017 Annual Meeting, held November 8–11 in Wailea, Hawaii.

The study used a two-stage design, where if enough early responses were seen then the second half of the cohort would be accrued. The trial opened in 2013, and four partial responses were reported by March of this year, leading to the opening of the second stage in April. Because accrual of these patients is difficult, the study opened at three additional sites in California.

To date, 45 patients have been accrued, across a variety of soft-tissue sarcoma subtypes. ASPS is the most common, with 6 patients, followed by myxofibrosarcoma and leiomyosarcoma with 5 patients.

Grade 3/4 adverse events attributed to cabozantinib that occurred in multiple patients included hypertension (21%), neutropenia (13%), abdominal pain (8%), lipase elevation (8%), and thromboembolic events (8%). There were single cases of left ventricular dysfunction, enterocolitis, fatigue, and several other adverse events. Eight patients required a cabozantinib dose reduction, and three patients needed two reductions.

The partial responses were seen in two ASPS patients, as well as one patient with extraskeletal myxoid chondrosarcoma, and one with myxoid liposarcoma. Three of the partial responders remain on treatment, Chen said.

“Cabozantinib has some activity” in soft-tissue sarcoma, Chen said, adding that more time is needed to assess most patients in the second stage of the study. The goal of the study is to continue accrual up to 50 patients.