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Cabozantinib induces promising response rate for soft tissue sarcoma
WAILEA, Hawaii — Patients with various subtypes of soft tissue sarcoma achieved partial response with cabozantinib, according to open-label phase 2 study results presented at the Connective Tissue Oncology Society Annual Meeting.
“There is increased VEGF expression in some patients with soft tissue sarcoma, which correlates with greater tumor burden and, possibly, growth,” Alice Chen, MD, director of the developmental therapeutics clinic at NCI, said during her presentation. “Various soft tissue sarcoma cell lines also have shown increased expression of c-MET. We hypothesized that if we could inhibit both c-MET and VEGF, we could see some activity using the drug cabozantinib (Cabometyx, Exelixis) a potent inhibitor of MET and VEGFR2.”
Chen and colleagues conducted a two-stage trial of cabozantinib monotherapy in patients with soft tissue sarcoma. Patients had alveolar soft part sarcoma (n = 6), leiomyosarcoma (n = 5), clear cell sarcoma (n = 3), liposarcoma (n = 2), synovial sarcoma (n = 2), embryonal sarcoma (n = 1), malignant peripheral nerve sheath tumor (n = 1), myxoid chondrosarcoma (n = 1), myoepithelioma (n = 1), myxoid cell sarcoma (n = 1) and gastrointestinal stromal tumor (n = 1).
Response rate and 6-months PFS rate served as the study’s primary endpoint. Researchers plan to evaluate circulating levels of hepatocyte growth factor, VEGF-A, soluble VEGFR2 and soluble MET pre- and posttreatment as a secondary endpoint among patients in the second stage of the study.
Patients received 60 mg oral cabozantinib daily for 28-day cycles. Researchers planned to open the second stage of the study if they observed four objective responses, or 13 patients with 6-month PFS in the first 25 patients.
At the time of the analysis, five patients remained on study. Duration of time on study ranged from 7 to 47 months.
Four patients achieved a partial response — two patients with alveolar soft part sarcoma, one patient with liposarcoma and one patient with myxoid chondrosarcoma — and researchers opened the second stage. Time to partial response ranged from 4 to 22 months, and response duration averaged 39 months.
Twelve patients had stable disease for 6 months, and median PFS was 9.6 months.
Treatment-related grade 3 to grade 4 adverse events included hypertension (21%), neutropenia (13%), abdominal pain (8%), lipase elevation (8%), thromboembolic events (8%), and one case each (4%) or left ventricular dysfunction, alkaline phosphatase elevation, enterocolitis, fatigue, mucositis, nausea, hand-foot syndrome and transaminitis.
Eight patients required dose reductions.
“Cabozantinib is well tolerated and has some activity; at least in this trial, we have passed our first stage into our second stage, and we have accrued 45 patients as of Sept. 30,” Chen said.
Most patients in the second stage are too early to assess, and pharmacodynamic studies are ongoing, she added. – by Alexandra Todak
Reference:
Chen A, et al. Abstract 013. Presented at: CTOS Annual Meeting; Nov. 8-11, 2017; Maui, Hawaii.
Disclosures: The authors report no relevant financial disclosures.