Chan John K, Deng Wei, Higgins Robert V, Tewari Krishnansu S, Bonebrake Albert J, Hicks Michael, Gaillard Stephanie, Ramirez Pedro T, Chafe Weldon, Monk Bradley J, Aghajanian Carol
Division of Gynecological Oncology, California Pacific-Palo Alto Medical Foundation, Sutter Cancer Research Institute, San Francisco, CA 94115, United States.
NRG Oncology/Gynecologic Oncology Group Statistics & Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
Gynecol Oncol. 2017 Sep;146(3):554-559. doi: 10.1016/j.ygyno.2017.05.033. Epub 2017 Jul 18.
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.
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.
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.
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.
布立尼布是一种口服的酪氨酸激酶抑制剂，可作用于血管内皮生长因子（VEGF）和成纤维细胞生长因子受体（FGFR）。我们研究了其在持续性或复发性宫颈癌患者中的疗效和耐受性。
符合条件的患者既往至少接受过一种用于复发且疾病可测量的细胞毒性治疗方案。每天口服布立尼布800mg（1个周期=28天），直至疾病进展或出现不可耐受的毒性。主要终点为无进展生存期（PFS）>6个月和客观肿瘤反应。
在纳入的28例符合条件且可评估的女性中，11例（39%）接受过初次手术，25例（89%）接受过既往放疗。18例（64%）接受过一次既往细胞毒性治疗，10例（36%）接受过2种既往治疗方案。12例（43%）接受布立尼布治疗>2个周期，4例（14%）接受治疗>10个周期（范围：1-20）。7例（25%）患者的PFS>6个月（90%CI：7.3%-33.9%）。2例（7%）（90%CI：1.3%-20.8%）患者出现部分肿瘤反应，持续时间分别为8个月和22个月，12例（43%）疾病稳定。中位PFS为3.2个月（90%CI：2.1-4.4）。中位总生存期为7.9个月（90%CI：6.1-11.7）。较常见的3级不良事件为高血压、贫血、低钠血症、高血糖、肝酶升高、恶心、头痛和结肠出血。4级不良事件包括脓毒症和高血压。
基于该II期试验的早期结果，布立尼布耐受性良好，在第一阶段显示出足够的活性，但由于药物供应不足试验提前终止。
