TKI Shows Promise in Sarcoma Study

Tivozanib was well-tolerated and showed promising antitumor activity in patients with soft tissue sarcoma overexpressing vascular endothelial growth factors (VEGF), supporting efforts for further research, according to a study published in Annals of Oncology.


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VEGF and VEGF-receptor activation have been associated with more aggressive sarcoma tumors. Tivozanib is a potent small molecule tyrosine kinase inhibitor against VEGF-receptors 1-3, with activity against PDGFRα/β and cKIT. It was originally developed for renal cell carcinoma, but failed to receive approval from the US Food and Drug Administration.

In a study led by Mark Agulnik, MD, Northwestern University (Chicago, IL), investigators performed a Simon two-stage phase II trial assessing use of tivozanib in patients with sarcoma when given orally at 1.5mg daily, 3 weeks on 1 week off, on a 28 day cycle until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) rate at 16 weeks. Researchers also analyzed overall survival, response rate, safety, and correlative studies.

A total of 58 patients with soft tissue sarcoma were enrolled in the trial and treated with tivozanib. Leiomyosarcoma was the most common soft tissue sarcoma subtype and 27 patients (46%) had received at least 3 lines of therapy prior to study entry. Forty-one percent of patients were treated with VEGF targeted therapies.

Overall, 2 patients achieved partial response and 30 had stable disease. The 16-week PFS rate was 35.4%, with a median PFS of 3.5 months. Median overall survival was 12.2 months. However, researchers were unable to identify any correlation between the expression of VEGF receptors, PDGFRα/β, or FGF and tivozanib activity.

The most common all-grade toxicities associated with tivozanib treatment were fatigue (48.3%), hypertension (43.1%), nausea (31%) and diarrhea (27.6%). Hypertension was the most common grade 3 toxicity, occurring in 22.4% of patients.

From these results, researchers concluded that tivozanib safely demonstrated antitumor activity in addition to a promising median PFS and PFS rate at 4 months in patients with pretreated, metastatic soft tissue sarcoma. More research is needed to determine the efficacy of tivozanib in this patient population.