Abstract
Objective: Tivozanib is a potent selective pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor with a long half-life. This study assessed its activity in patients with recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer (OC). Methods: This open-label phase II study used a Simon's two-stage design. Eligible patients had recurrent, platinum-resistant OC and measurable or detectable disease. There was no limit on the number of prior regimens. Treatment consisted of tivozanib 1.5 mg orally once daily for 21 days in a 28-day cycle. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity assessment. Results: Thirty-one patients were enrolled, and 30 were treated. The median age was 59.5 years, and median number of prior regimens was 4 (range 1–9). Twenty-four patients were evaluable for response, and four (16.7%) achieved a partial response (PR; ORR = 16.7%). An additional fourteen (58.3%) patients had stable disease (SD). The clinical benefit rate (PR + SD) was 75.0%, and the median duration of objective response was 5.7 months. For all patients on trial, the median PFS was 4.1 months (95% confidence interval (CI): 1.7–5.8) and OS 8.6 months (95% CI: 5.4–12.5). There were no treatment-related deaths. Serious adverse events occurred in 13.3% of patients and included small intestinal perforation or obstruction and stroke. Grade 3–4 adverse events occurred in 60% of patients, including hypertension (26.7%) and fatigue (10%). Conclusions: Tivozanib is effective in patients with recurrent OC, with moderate toxicity and no treatment-related deaths, supporting its further development.
Original language | English (US) |
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Pages (from-to) | 57-63 |
Number of pages | 7 |
Journal | Gynecologic oncology |
Volume | 163 |
Issue number | 1 |
DOIs | |
State | Published - Oct 2021 |
Funding
This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program (ORP) from general research support provided by AVEO. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA060553 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We appreciate the support from the Clinical Trial Office of the Robert H Lurie Comprehensive Cancer Center . We acknowledge contributions from Drs. Latoya Perry, Alok Pant, Julian Schink, as well as Karen Novak, APN and Nancy Anderson, APN.
Keywords
- Antiangiogenesis
- Ovarian cancer
- Phase II trial
- Platinum-resistant
- Tivozanib
ASJC Scopus subject areas
- Obstetrics and Gynecology
- Oncology