Journal article
A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study
Gynecologic Oncology, Vol.135(1), pp.38-43
10/2014
DOI: 10.1016/j.ygyno.2014.07.083
PMCID: PMC4278402
PMID: 25019571
Abstract
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). 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 800mg 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 64years. 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 10.7months, 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. •Brivanib is an oral agent with activity against VEGF and FGFR, both important targets in endometrial cancer.•Of 43 evaluable patients, eight (18.6%) had responses and 13 patients (30.2%) were PFS at 6months.•Brivanib is worthy of further investigation based on PFS at six months.
Details
- Title: Subtitle
- A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study
- Creators
- Matthew A Powell - OB/GYN, Washington University School of Medicine, St. Louis, MO 63110, USAMichael W Sill - Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USAPaul J Goodfellow - Obstetrics and Gynecology, Ohio State University, Columbus, OH, USADoris M Benbrook - University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USAHeather A Lankes - Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USAKimberly K Leslie - Department of Obstetrics & Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USAYvette Jeske - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, AustraliaRobert S Mannel - University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USAMonique A Spillman - OB/GYN, University of Colorado, Denver, CO 80045, USAPaula S Lee - Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USAJames S Hoffman - The Hospital of Central Connecticut, New Britain, CT 06050, USAD. Scott McMeekin - University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USAPamela M Pollock - Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
- Resource Type
- Journal article
- Publication Details
- Gynecologic Oncology, Vol.135(1), pp.38-43
- DOI
- 10.1016/j.ygyno.2014.07.083
- PMID
- 25019571
- PMCID
- PMC4278402
- NLM abbreviation
- Gynecol Oncol
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Publisher
- Elsevier Inc
- Grant note
- P50 CA134254; CA27469; 2R01CA99908 / NIH (http://dx.doi.org/10.13039/100000002) 1 U10 CA180822 / NRG Oncology Grant 27469; CA 37517; U24 CA114793 / National Cancer Institute (http://dx.doi.org/10.13039/100000054)
- Language
- English
- Date published
- 10/2014
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9983930283302771
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