John K Chan1, Wei Deng2, Robert V Higgins3, Krishnansu S Tewari4, Albert J Bonebrake5, Michael Hicks6, Stephanie Gaillard7, Pedro T Ramirez8, Weldon Chafe9, Bradley J Monk10, Carol Aghajanian11. 1. Division of Gynecological Oncology, California Pacific-Palo Alto Medical Foundation, Sutter Cancer Research Institute, San Francisco, CA 94115, United States. Electronic address: chanjohn@sutterhealth.org. 2. NRG Oncology/Gynecologic Oncology Group Statistics & Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Electronic address: wdeng@gogstats.org. 3. Division of Gynecological Oncology, Levine Cancer Institute, Charlotte, NC 28203, United States. Electronic address: robert.higgins@carolinashealthcare.org. 4. Division of Gynecological Oncology, University of California, Irvine Medical Center, Orange, CA 92868, United States. Electronic address: ktewari@uci.edu. 5. Division of Gynecological Oncology, Cancer Research for the Ozarks-Cox Health, Springfield, MO 65807, United States. Electronic address: albert.bonebrake@coxhealth.com. 6. Division of Gynecological Oncology, Michigan Cancer Research Consortium, Pontiac, MI 48341, United States. Electronic address: mrhicks2pc@gmail.com. 7. Division of Medical Oncology, Duke University Medical Center, Durham, NC 27710, United States. Electronic address: stephanie.gaillard@duke.edu. 8. Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. Electronic address: peramire@mdanderson.org. 9. Division of Gynecological Oncology, Virginia Commonwealth University, Richmond, VA 23298, United States. Electronic address: wechafe@vcu.edu. 10. Division of Gynecological Oncology, Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine at St. Joseph's Hospital, Phoenix, AZ 85016, United States. Electronic address: Bradley.Monk@usoncology.com. 11. Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, United States. Electronic address: aghajanc@mskcc.org.
Abstract
BACKGROUND: Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients. METHODS: Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) >6months and objective tumor response. RESULTS: Of 28 eligible and evaluable women enrolled, 11 (39%) had primary surgery and 25 (89%) had prior radiation. Eighteen (64%) received one prior cytotoxic treatment and 10 (36%) had 2 prior regimens. Twelve (43%) had >2cycles of brivanib with 4 (14%) receiving >10cycles (range: 1-20). Seven (25%) patients had PFS >6months (90% CI: 7.3%-33.9%). Two (7%) (90% CI: 1.3%-20.8%) patients had partial tumor response with duration of 8 and 22months and 12 (43%) had stable disease. The median PFS was 3.2months (90% CI: 2.1-4.4). The median overall survival was 7.9months (90% CI: 6.1-11.7). More common grade 3 adverse events were hypertension, anemia, hyponatremia, hyperglycemia, elevated liver enzymes, nausea, headache, and colon hemorrhage. Grade 4 adverse events included sepsis and hypertension. CONCLUSIONS: Based on early results of this phase II trial, brivanib was well tolerated and demonstrated sufficient activity after first stage but trial was stopped due to lack of drug availability.
BACKGROUND:Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancerpatients. METHODS: Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) >6months and objective tumor response. RESULTS: Of 28 eligible and evaluable women enrolled, 11 (39%) had primary surgery and 25 (89%) had prior radiation. Eighteen (64%) received one prior cytotoxic treatment and 10 (36%) had 2 prior regimens. Twelve (43%) had >2cycles of brivanib with 4 (14%) receiving >10cycles (range: 1-20). Seven (25%) patients had PFS >6months (90% CI: 7.3%-33.9%). Two (7%) (90% CI: 1.3%-20.8%) patients had partial tumor response with duration of 8 and 22months and 12 (43%) had stable disease. The median PFS was 3.2months (90% CI: 2.1-4.4). The median overall survival was 7.9months (90% CI: 6.1-11.7). More common grade 3 adverse events were hypertension, anemia, hyponatremia, hyperglycemia, elevated liver enzymes, nausea, headache, and colon hemorrhage. Grade 4 adverse events included sepsis and hypertension. CONCLUSIONS: Based on early results of this phase II trial, brivanib was well tolerated and demonstrated sufficient activity after first stage but trial was stopped due to lack of drug availability.
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