Journal article
A phase II study of tivozanib in patients with metastatic and nonresectable soft-tissue sarcomas
Annals of oncology, Vol.28(1), pp.121-127
01/2017
DOI: 10.1093/annonc/mdw444
PMCID: PMC6246191
PMID: 27771610
Abstract
Soft tissue sarcomas (STSs) overexpress vascular endothelial growth factors (VEGF) and VEGF-receptors (VEGFR) activation have been associated with tumor aggressiveness. Tivozanib is a potent small molecule tyrosine kinase inhibitor against VEGFR1-3, with activity against PDGFRα/β and cKIT. The primary endpoint of this study was progression free survival (PFS) rate at 16 weeks. Secondary end points were overall survival (OS), response rate, safety and correlative studies.
A Simon two-stage phase II trial was performed using tivozanib given orally at 1.5mg daily, 3 week on 1 week off on a 28day cycle until disease progression or intolerable toxicity.
Fifty-eight patients were enrolled and treated with tivozanib. Leiomyosarcoma was the most common STS histological type in our cohort (47%) and 27 patients (46%) had received at least 3 lines of therapy prior to study entry. Up to 24 patients (41%) had prior VEGF targeted therapies. Partial response and stable disease were observed in 2 (3.6%) and 30 (54.5%) patients. The 16 week PFS rate was 36.4% [95% confidence interval (CI) 23.7–49.1] and a median PFS of 3.5 months (95% CI 1.8–3). Median OS observed was 12.2 months (95% CI 8.1–16.8). The most frequent all grade toxicities were fatigue (48.3%), hypertension (43.1%), nausea (31%) and diarrhea (27.6%). The most common grade three toxicity was hypertension (22.4%). Correlative studies demonstrate no correlation between the expression of VEGFR 1, 2 or 3, PDGFRα/β or FGF, and activity of tivozanib.
Tivozanib was well tolerated and showed antitumor activity with a promising median PFS and PFS rate at 4 months in a heavily pretreated population of metastatic STSs. Our results support further studies to assess the clinical efficacy of tivozanib in STS.
NCT01782313
Details
- Title: Subtitle
- A phase II study of tivozanib in patients with metastatic and nonresectable soft-tissue sarcomas
- Creators
- M. Agulnik - Northwestern UniversityR.L.B. Costa - Northwestern UniversityM. Milhem - University of IowaA.W. Rademaker - Northwestern UniversityB.C. Prunder - Washington University in St. LouisD. Daniels - Washington University in St. LouisB.T. Rhodes - Washington University in St. LouisC. Humphreys - Northwestern UniversityS. Abbinanti - Northwestern UniversityL. Nye - Northwestern UniversityR. Cehic - Northwestern UniversityA. Polish - Northwestern UniversityC. Vintilescu - Northwestern UniversityT. McFarland - University of Wisconsin–MadisonK. Skubitz - University of MinnesotaS. Robinson - Mayo ClinicS. Okuno - Division of Hematology/Oncology, Mayo Clinic, Rochester, USA.B.A. Van Tine - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Annals of oncology, Vol.28(1), pp.121-127
- Publisher
- Elsevier Ltd
- DOI
- 10.1093/annonc/mdw444
- PMID
- 27771610
- PMCID
- PMC6246191
- ISSN
- 0923-7534
- eISSN
- 1569-8041
- Grant note
- name: Northwestern Memorial Foundation, DeBoer Family Sarcoma Research Grant Initiative
- Language
- English
- Date published
- 01/2017
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359937702771
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