Bell-McGuinn Katherine M, Konner Jason A, Tew William P, Hensley Martee L, Iasonos Alexia, Charpentier Eric, Mironov Svetlana, Sabbatini Paul, Aghajanian Carol
Departments of *Medicine and †Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY; ‡Sanofi Statistics Department, Cambridge MA; and §Department of Radiology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
Int J Gynecol Cancer. 2016 Feb;26(2):255-60. doi: 10.1097/IGC.0000000000000591.
The aim of the study was to evaluate the activity and tolerability of iniparib monotherapy in women with BRCA1 or BRCA2-associated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Eligible patients had advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, germline BRCA1 or BRCA2 mutation, measurable disease, and at least 1 previous treatment regimen of platinum/taxane chemotherapy. Patients received iniparib 8 mg/kg intravenously on days 1 and 4 weekly, with imaging every 8 weeks. Treatment continued until disease progression or adverse events (AEs) prohibited further therapy. Common Terminology Criteria for AEs v3.0 was used to grade AEs. The primary endpoint was tumor response. The study was conducted with a Simon 2-stage design with 12 and 23 patients planned in the first and second stage, respectively. The study was designed to distinguish between 10% and 30% responding with types 1 and 2 error of 0.10.
Twelve patients were treated on study, with median exposure to iniparib of 7.5 weeks. The median number of previous chemotherapeutic regimens was 7. Treatment-related AEs (≥10%) included asthenia (83.3%), constipation (25%), diarrhea (25%), nausea (25%), abdominal pain (16.7%), and decreased hemoglobin (16.7%). All treatment-related AEs were grades 1 or 2 with the following 2 exceptions: 1 grade 3 diarrhea and 1 grade 3 hypertension. One patient had stable disease lasting 2 cycles; the remaining 11 patients had progressive disease. The study did not proceed to second stage enrollment.
Iniparib did not show significant activity in this heavily pretreated ovarian cancer population, all of whom had BRCA1 or BRCA2 mutations.
本研究旨在评估尼帕利布单药治疗携带BRCA1或BRCA2基因相关的晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌女性患者的活性和耐受性。
符合条件的患者患有晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌，存在种系BRCA1或BRCA2突变，疾病可测量，且既往至少接受过1个铂类/紫杉烷化疗方案。患者在第1天和第4天每周静脉注射尼帕利布8mg/kg，每8周进行一次影像学检查。治疗持续至疾病进展或出现不良事件（AE）而禁止进一步治疗。采用不良事件通用术语标准v3.0对AE进行分级。主要终点为肿瘤反应。本研究采用西蒙两阶段设计，第一阶段和第二阶段分别计划入组12例和23例患者。该研究旨在区分10%和30%的缓解率，Ⅰ类和Ⅱ类错误率均为0.10。
12例患者接受了研究治疗，尼帕利布的中位暴露时间为7.5周。既往化疗方案的中位数为7个。与治疗相关的AE（≥10%）包括乏力（83.3%）、便秘（25%）、腹泻（25%）、恶心（25%）、腹痛（16.7%）和血红蛋白降低（16.7%）。所有与治疗相关的AE均为1级或2级，以下2例除外：1例3级腹泻和1例3级高血压。1例患者疾病稳定持续2个周期；其余11例患者疾病进展。该研究未进入第二阶段入组。
在这个均携带BRCA1或BRCA2突变且接受过大量治疗的卵巢癌患者群体中，尼帕利布未显示出显著活性。
