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Clinical Trial
. 2020 Jun;157(3):585-592.
doi: 10.1016/j.ygyno.2019.10.014. Epub 2020 Apr 1.

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  1 , G R Petroni  2 , N Varhegyi  2 , J Brown  3 , D Jelovac  4 , K N Moore  5 , W P McGuire  6 , C Darus  7 , L M Barroilhet  8 , A A Secord  9
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Clinical Trial

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 et al. Gynecol Oncol. 2020 Jun.

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/m2 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.

Keywords: Angiogenesis; Gemcitabine; Ovarian cancer; Pazopanib.

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Conflict of interest statement

Declaration of competing interest Dr. Duska has served on advisory boards for Astra Zeneca, Genentech, Merck, Tesaro, Morphotek. She serves on the DSMC for an Inovio trial. She has received research funding from GSK/Novartis (current trial) and Merck. Her instition has received research funding from multiple pharmaceutical companies. Dr. Secord reports research funding from pharmaceutical companies outside the submitted work; and a grant from the National Cancer Trial Network outside the submitted work. She also reports honoraria/advisory boards from Alexion, Aravive, Astex Pharmaceuticals Inc., Astra Zeneca, Clovis, Janssen/Johnson & Johnson, Merck, Mersana, Myriad, Oncoquest, Roche/Genentech, and Tesaro outside of the submitted work. Dr. Moore has served on advisory boards for Astra Zeneca, Advaxis, Clovis, Immunogen, Tesaro, Genentech/Roche, Janssen, Pfizer, Merck, Aravive, Samumed, Oncomed, VBL Therapeutics and Eisai. She serves on steering committees (not compensated) for Astra Zeneca, Tesaro, VBL Therapeutics. She has received research funding from PTC Therapeutics, Lilly, Genentech/Roche and Clovis. Dr. Brown reports personal fees from Tesaro, personal fees from Clovis, from Tempus, personal fees from AstraZeneca, personal fees from Genentech, personal fees from Olympus, personal fees from Advanced Surgical Concepts, personal fees from OncLive, outside the submitted work. The following authors report no financial interests: Dr. McGuire, Dr. Petroni, Ms Varhegyi, Dr. Barroilhet, Dr. Jelovac, Dr. Darus.

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