TY - JOUR
T1 - A phase II evaluation of brivanib in the treatment of persistent or recurrent carcinoma of the cervix
T2 - An NRG Oncology/Gynecologic Oncology Group study
AU - Chan, John K.
AU - Deng, Wei
AU - Higgins, Robert V.
AU - Tewari, Krishnansu S.
AU - Bonebrake, Albert J.
AU - Hicks, Michael
AU - Gaillard, Stephanie
AU - Ramirez, Pedro T.
AU - Chafe, Weldon
AU - Monk, Bradley J.
AU - Aghajanian, Carol
N1 - Funding Information:
Funded by the National Cancer Institute and BMS; ClinicalTrials.gov number, NCT01267253 (BMS Study CA182-048). This work was also supported by National Cancer Institute grants to NRG Oncology (1U10 CA180822) and NRG Operations (U10CA180868).
Publisher Copyright:
© 2017
PY - 2017/9
Y1 - 2017/9
N2 - 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 800 mg was administered orally every day (1 cycle = 28 days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) > 6 months 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 > 2 cycles of brivanib with 4 (14%) receiving > 10 cycles (range: 1–20). Seven (25%) patients had PFS > 6 months (90% CI: 7.3%–33.9%). Two (7%) (90% CI: 1.3%–20.8%) patients had partial tumor response with duration of 8 and 22 months and 12 (43%) had stable disease. The median PFS was 3.2 months (90% CI: 2.1–4.4). The median overall survival was 7.9 months (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.
AB - 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 800 mg was administered orally every day (1 cycle = 28 days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) > 6 months 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 > 2 cycles of brivanib with 4 (14%) receiving > 10 cycles (range: 1–20). Seven (25%) patients had PFS > 6 months (90% CI: 7.3%–33.9%). Two (7%) (90% CI: 1.3%–20.8%) patients had partial tumor response with duration of 8 and 22 months and 12 (43%) had stable disease. The median PFS was 3.2 months (90% CI: 2.1–4.4). The median overall survival was 7.9 months (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.
KW - Brivanib
KW - Recurrent cervical carcinoma
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U2 - 10.1016/j.ygyno.2017.05.033
DO - 10.1016/j.ygyno.2017.05.033
M3 - Article
C2 - 28728751
AN - SCOPUS:85024491542
SN - 0090-8258
VL - 146
SP - 554
EP - 559
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 3
ER -