title: A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.
authors.affiliation: OB/GYN, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: powellm@wudosis.wustl.edu.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Powell
authors.affiliation: Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Electronic address: msill@gogstats.org.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.affiliation: Obstetrics and Gynecology, Ohio State University, Columbus, OH, USA. Electronic address: paul.goodfellow@osumc.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Goodfellow
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. Electronic address: doris-benbrook@ouhsc.edu.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Benbrook
authors.affiliation: Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Electronic address: hlankes@gogstats.org.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lankes
authors.affiliation: Department of Obstetrics & Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. Electronic address: kimberly-leslie@uiowa.edu.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Leslie
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Jeske
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. Electronic address: Robert-mannel@ouhsc.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.affiliation: OB/GYN, University of Colorado, Denver, CO 80045, USA. Electronic address: monique.spillman@ucdenver.edu.
authors.forename: Monique A
authors.initials: MA
authors.lastname: Spillman
authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: lee00139@mc.duke.edu.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Lee
authors.affiliation: The Hospital of Central Connecticut, New Britain, CT 06050, USA. Electronic address: james.hoffman@hhchealth.org.
authors.forename: James S
authors.initials: JS
authors.lastname: Hoffman
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. Electronic address: scott-mcmeekin@ouhsc.edu.
authors.forename: D Scott
authors.initials: DS
authors.lastname: McMeekin
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. Electronic address: Pamela.pollock@qut.edu.au.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Pollock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D014227:Triazines / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014227:Triazines; D042461:Vascular Endothelial Growth Factor A; C509922:brivanib; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D000409:Alanine
keywords: Brivanib; Endometrial cancer