A randomized phase II evaluation of weekly gemcitabine plus pazopanib versus weekly gemcitabine alone in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma

L R. Duska, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA. Electronic address: lduska@virginia.edu.
G R. Petroni, Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA.
N Varhegyi, Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA.
J Brown, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Levine Cancer Institute, Charlotte, NC, USA.
D Jelovac, Department of Medicine, Division of Medical Oncology. Johns Hopkins University, Baltimore, MD, USA.
K N. Moore, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
W P. McGuire, Virginia Commonwealth University, Richmond, VA, USA.
C Darus, Maine Medical Center, Portland, ME, USA.
L M. Barroilhet, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology. Univeristy of Wisconsin, Madison, WI, USA.
A A. Secord, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology. Duke Unviersity Medical Center, Durham, NC, USA.

Abstract

OBJECTIVE: Angiogenesis inhibition is a valuable strategy for ovarian cancer (EOC). Pazopanib (paz) is a potent small molecular inhibitor of VEGF-1, -2, -3, PDGFR, c-kit, and has activity as a single agent in ovarian cancer. We designed a trial to assess the benefit of adding paz to gemcitabine (gem) in patients with recurrent EOC. METHODS: An open-label, randomized, multi-site, phase 2 trial was conducted (NCT01610206) including patients with platinum resistant or sensitive disease, ≤ 3 prior lines of chemotherapy, and measurable/evaluable disease. Patients were randomly assigned to weekly gem 1000 mg/m on days 1 and 8 of a 21 day cycle, with or without paz 800 mg QD, stratified by platinum sensitivity and number of prior lines (1 vs 2 or 3). The primary endpoint was PFS. RESULTS: 148 patients were enrolled 2012-2017. Median age was 63 years (30-82); 60% were platinum resistant; median surveillance was 13 months (0.4-54 months). Median PFS was 5.3 (95% CI, 4.2-5.8) vs 2.9 months (95% CI, 2.1-4.1) in the gem arm. The PFS effect was most pronounced in the platinum resistant group (5.32 vs 2.33 months Tarone-Ware p < 0.001). There was no difference in OS. Overall RR (PR 20% vs 11%, Chi-squre p = 0.02) and DCR (80% vs 60%, Chi-square p < 0.001) were higher in the combination. High grade AEs in the combination arm included ≥ Grade 3: hypertension (15%), neutropenia (35%), and thrombocytopenia (12%). CONCLUSIONS: The addition of paz to gem enhanced anti-tumor activity; those with platinum-resistant disease derived the most benefit from combination therapy, even in the setting of receiving prior bevacizumab.