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

• Published in: Gynecologic oncology 2021-10, Vol.163 (1), p.57-63
• Main Authors: Cowan, Mathew, Swetzig, Wendy M., Adorno-Cruz, Valery, Pineda, Mario J., Neubauer, Nikki L., Berry, Emily, Lurain, John R., Shahabi, Shohreh, Taiym, Deanna, Nelson, Valerie, O'Shea, Kaitlyn Lucrezia, Kocherginsky, Masha, Matei, Daniela
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antiangiogenesis; Drug Resistance, Neoplasm; Fallopian Tube Neoplasms - drug therapy; Fallopian Tube Neoplasms - mortality; Female; Humans; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - mortality; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - mortality; Phase II trial; Phenylurea Compounds - adverse effects; Phenylurea Compounds - therapeutic use; Platinum - therapeutic use; Platinum-resistant; Quinolines - adverse effects; Quinolines - therapeutic use; Tivozanib
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2021.08.005

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). 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. 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%). Tivozanib is effective in patients with recurrent OC, with moderate toxicity and no treatment-related deaths, supporting its further development. •Tivozanib is a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor.•Response rate to Tivozanib in platinum-resistant ovarian cancer is 16.7%; median progression-free survival is 4.1 months.•The most common adverse events were fatigue and hypertension.