Efficacy and safety of tivozanib in recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.

person Wendy M Swetzig Northwestern University Feinberg School of Medicine, Chicago, IL info_outline Wendy M Swetzig, John Robert Lurain, Emily Berry, Mario Javier Pineda, Shohreh Shahabi, LaToya Perry, Nikki Lynn Neubauer, Wilberto Nieves-Neira, Julian C. Schink, Alissa Schiller, Karen Novak, Nancy Jean Anderson, Kirsten Bell Burdett, Anna Everett Strohl, Masha Kocherginsky, Daniela Matei

Authors person Wendy M Swetzig Northwestern University Feinberg School of Medicine, Chicago, IL info_outline Wendy M Swetzig, John Robert Lurain, Emily Berry, Mario Javier Pineda, Shohreh Shahabi, LaToya Perry, Nikki Lynn Neubauer, Wilberto Nieves-Neira, Julian C. Schink, Alissa Schiller, Karen Novak, Nancy Jean Anderson, Kirsten Bell Burdett, Anna Everett Strohl, Masha Kocherginsky, Daniela Matei Organizations Northwestern University Feinberg School of Medicine, Chicago, IL, Northwestern Medicine Regional Medical Group, Warrenville, IL, Northwestern Medical Group, Chicago, IL Abstract Disclosures Research Funding Other Background: Tivozanib is a potent, selective pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor with a long half-life. This study assessed its activity in patients with recurrent, platinum-resistant ovarian cancer (OC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC). Methods: This open-label phase II study used a Simon’s two-stage design. Eligible patients had recurrent, platinum-resistant OC, FTC or PPC; ECOG PS of 0-1; normal end organ function; 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 (3 weeks on/1 week off). The primary endpoint was response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity assessment. If 1 partial response (PR) was observed in stage I [n = 12], enrollment proceeded to stage II. The null hypothesis was rejected for ≥ 4 responses in 30 patients. Results: Thirty-one patients were enrolled, and 30 were treated. Twenty-three had OC [76.67%], 5 FTC [16.67%] and 2 PPC [6.67%]. Twenty-six had measurable [86.67%] and 4 detectable disease [13.37%]. The median age was 60, and median number of prior regimens was 4 [range 1-9]. Four PRs [13.33%] were recorded. Twelve patients had stable disease (SD) [40%]. The clinical benefit rate (PR + SD) was 53%. Seven patients [23.33%] survived progression-free for > 6 mos. One patient continued treatment for > 2 yrs. The median PFS was 4 mos [range 1-25] and median OS was 8 mos [range 1-39]. There were no treatment-related deaths. Grade 3-4 related toxicities were hypertension [8], fatigue [3], fistula [2], hyponatremia [2], intestinal perforation, obstruction, stroke, proteinuria, hypomagnesemia, hypoalbuminemia, portal hypertension, nausea and anemia [1 each]. Frequent grade 1-2 related toxicities included fatigue [19], hypertension [13], anorexia [12], arthralgia [11], diarrhea [11], weight loss [10], hoarseness [8], headache [8] and nausea [7]. Exploratory analyses in tumor samples are ongoing. Conclusions: Tivozanib is active in patients with recurrent OC, FTC or PPC, without substantial toxicity, supporting its further development. Clinical trial information: NCT01853644