Tivozanib demonstrated antitumor activity and was well-tolerated among heavily pretreated patients with metastatic soft tissue sarcoma, according to a study published in the Annals of Oncology.1

Soft tissue sarcomas overexpress vascular endothelial growth factors (VEGF), and the activation of VEGF receptors (VEGFR) is associated with more aggressive tumors. Tivozanib is a potent tyrosine kinase inhibitor that blocks the activity of VEGFR1, VEGFR2, VEGFR3, PDGFRα/β, and cKIT. Researchers therefore evaluated the tolerability and activity of tivozanib in patients with metastatic and non-resectable soft tissue sarcoma.

For the 2-stage, open-label, phase 2 trial (ClinicalTrials.gov Identifier: NCT01782313), investigators enrolled 58 patients with metastatic, locally advanced, or locally recurrent soft tissue sarcoma to receive tivozanib orally daily for 21 days of each 4-week cycles until disease progression or unacceptable toxicity. Of those, 47% had leiomyosarcoma, 46% had received at least 3 prior lines of therapy, and 41% had received prior VEGF-targeted therapies.

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Median follow-up was 9.6 months; results showed that 3.6% achieved partial responses and 54.5% had stable disease. No complete responses were observed.

Researchers found that the progression-free survival rate at 16 weeks was 36.4% (95% CI, 23.7-49.1) and median progression-free survival was 3.5 months (95% CI, 1.8-3). Median overall survival was 12.2 months (95% CI, 8.1-16.8).

For comparison, treatment with pazopanib in the phase 3 PALETTE trial demonstrated a median progression-free survival of 4.6 months (95% CI, 3.7-4.8) in patients with advanced soft tissue sarcoma. A phase 2 trial of pazopanib showed a 12-week progression-free survival rate of approximately 40% among pretreated patients.

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The most common adverse events were fatigue, hypertension, nausea, and diarrhea. The most frequently reported grade 3 toxicity was hypertension, which was observed in approximately 22% of patients.

Further clinical trials are warranted to determine the optimal role of tivozanib in patients with soft tissue sarcoma.


  1. Agulnik M, Costa RL, Milhem M, et al. A phase II study of tivozanib in patients with metastatic and nonresectable soft-tissue sarcomas. Ann Oncol. 2016 Oct 22. doi: 10.1093/annonc/mdw444 [Epub ahead of print]