A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG oncology/gynecologic oncology group study
Powell, Matthew A., Sill, Michael W., Goodfellow, Paul J., Benbrook, Doris M., Lankes, Heather A., Leslie, Kimberly K., Jeske, Yvette, Mannel, Robert S., Spillman, Monique A., Lee, Paula S., Hoffman, James S., McMeekin, D. Scott, & Pollock, Pamela M. (2014) A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG oncology/gynecologic oncology group study. Gynecologic Oncology, 135(1), pp. 38-43.
Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC).
PATIENTS AND METHODS
Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and performance status of ≤2. Treatment consisted of brivanib 800 mg orally every day until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at six months and objective tumor response. Expression of multiple angiogenic proteins and FGFR2 mutation status was assessed.
Forty-five patients were enrolled. Forty-three patients were eligible and evaluable. Median age was 64 years. Twenty-four patients (55.8%) received prior radiation. Median number of cycles was two (range 1-24). No GI perforations but one rectal fistula were seen. Nine patients had grade 3 hypertension, with one experiencing grade 4 confusion. Eight patients (18.6%; 90% CI 9.6%-31.7%) had responses (one CR and seven PRs), and 13 patients (30.2%; 90% CI 18.9%-43.9%) were PFS at six months. Median PFS and overall survival (OS) were 3.3 and 10.7 months, respectively. When modeled jointly, VEGF and angiopoietin-2 expression may diametrically predict PFS. Estrogen receptor-α (ER) expression was positively correlated with OS.
Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.
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|Item Type:||Journal Article|
|Keywords:||Brivanib; Endometrial cancer|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health|
|Copyright Owner:||Copyright 2014 Elsevier|
|Copyright Statement:||This is the author’s version of a work that was accepted for publication in Gynecologic Oncology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Gynecologic Oncology, [VOL 135, ISSUE 1, (2014)] DOI: 10.1016/j.ygyno.2014.07.083|
|Deposited On:||18 May 2015 02:55|
|Last Modified:||04 Nov 2015 14:42|
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