Efficacy and safety of tivozanib in recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer, an NCCN phase II trial

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.