A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study

Abstract

Purpose: 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.

Results: 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.

Conclusion: Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.

Keywords: Brivanib; Endometrial cancer.

Conflict of interest statement

CONFLICT OF INTEREST

Dr. Matthew Powell is a consultant for Genentech, Eisei, and Arno Therapeutics.

Dr. Doris Benbrook received payment for consulting service as a Scientific Expert Witness in a bexarotene patent litigation case by Banner Pharmacaps Inc. and Mylan Inc. through Haynes and Boone, LLC. Travel during this service was reimbursed.

Dr. Pamela Pollock is a member of advisory board for Phase III trial planning for Doritinib (travel and accommodations paid for by Novartis).

Copyright © 2014. Published by Elsevier Inc.

Figures

Figure 1

Progression-free and overall survival for the 43 evaluable patients Progression-free survival (PFS) and overall survival (OA) for patients treated with brivanib. The median PFS was 3.3 months (90% CI 2.0 – 3.9 months). The median OS was 10.7 months (90% CI 9.2 – 18.1 months).