Matthew A Powell1, Michael W Sill2, Paul J Goodfellow3, Doris M Benbrook4, Heather A Lankes5, Kimberly K Leslie6, Yvette Jeske7, Robert S Mannel8, Monique A Spillman9, Paula S Lee10, James S Hoffman11, D Scott McMeekin12, Pamela M Pollock13. 1. OB/GYN, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: powellm@wudosis.wustl.edu. 2. Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Electronic address: msill@gogstats.org. 3. Obstetrics and Gynecology, Ohio State University, Columbus, OH, USA. Electronic address: paul.goodfellow@osumc.edu. 4. University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. Electronic address: doris-benbrook@ouhsc.edu. 5. Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Electronic address: hlankes@gogstats.org. 6. Department of Obstetrics & Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. Electronic address: kimberly-leslie@uiowa.edu. 7. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. 8. University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. Electronic address: Robert-mannel@ouhsc.edu. 9. OB/GYN, University of Colorado, Denver, CO 80045, USA. Electronic address: monique.spillman@ucdenver.edu. 10. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: lee00139@mc.duke.edu. 11. The Hospital of Central Connecticut, New Britain, CT 06050, USA. Electronic address: james.hoffman@hhchealth.org. 12. University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA. Electronic address: scott-mcmeekin@ouhsc.edu. 13. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. Electronic address: Pamela.pollock@qut.edu.au.
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.
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.
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