A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer
A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer
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DOI：
10.1016/j.ygyno.2014.07.003
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发表时间：
2014-10-01
影响因子：
4.7
通讯作者：
Wenham, Robert M.
中科院分区：
文献类型：
--
作者：
Vergote, Ignace;Schilder, Russell J.;Wenham, Robert M.
Objective.研究曲巴纳尼联合聚乙二醇脂质体阿霉素（PLD）或拓扑替康治疗复发性铂类耐药或部分铂类敏感性卵巢癌的耐受性和抗肿瘤活性。在这项开放标签的1b期研究中，患者接受曲巴纳尼10 mg/kg或15 mg/kg IV QW + PLD 50 mg/m2（分别为队列A1和A3）或托泊替康4 mg/m2（分别为队列B1和B3）。终点为剂量限制性毒性（DLT;主要）、治疗后出现的不良事件（AE）、总体应答率、抗曲巴纳尼抗体和药代动力学（次要）。103例患者入组。A1和B1中的1例患者发生DLT。在所有队列中，最常见的AE为恶心、疲乏和外周水肿。在两个trebananib + PLD队列（A1/A3）中，4级AE为肺栓塞、疾病进展和贫血。2例患者发生5级肠穿孔（n = 1）和猝死（n = 1）。在两个曲巴那尼+托泊替康队列（B1/B3）中，4级AE为中性粒细胞减少、低钾血症、粒细胞计数降低、胸痛、呼吸困难、中性粒细胞计数降低和肺栓塞。2例患者发生5级疾病进展。1例患者出现5级胸腔积液伴疾病进展。确认的客观缓解率为36.0%（A1）、34.8%（A3）、16.7%（B1）和0.0%（B3）。中位无进展生存期（月）分别为7.4（A1）、7.1（A3）、3.5（B1）和3.1（B3）。无明显药物间相互作用。Trebananib 10 mg/kg和15 mg/kg IV QW加PLD或托泊替康似乎在复发性铂耐药或部分铂敏感性卵巢癌中具有可接受的毒性特征。所有队列的抗肿瘤活性均明显。(C)2014 Elsevier Inc. All rights reserved.
Objective. To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.Methods. In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QW plus PLD 50 mg/m(2) (cohorts A1 and A3, respectively) or topotecan 4 mg/m(2) (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary).Results. 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n = 1) and sudden death (n = 1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent.Conclusions. Trebananib 10 mg/kg and 15 mg/kg IV QW plus PLD or topotecan appear to have acceptable toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Antitumor activity was evident across all cohorts. (C) 2014 Elsevier Inc. All rights reserved.