A Phase II Trial of Ziv-Aflibercept in Patients With Advanced Pancreatic Neuroendocrine Tumors

被引:6
作者
Halperin, Daniel M. [1 ]
Lee, J. Jack [2 ]
Ng, Chaan S. [3 ]
Strosberg, Jonathan R. [4 ]
Estrella, Jeannelyn S. [5 ]
Dagohoy, Cecile G. [1 ]
Dasari, Arvind [1 ]
Yao, James C. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA
[4] H Lee Moffitt Canc Ctr & Res Inst, Dept Gastrointestinal Oncol, Tampa, FL USA
[5] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
关键词
angiogenesis; clinical trial; neuroendocrine tumor; ziv-aflibercept; ENDOTHELIAL GROWTH-FACTOR; COMPUTED-TOMOGRAPHY; LIVER METASTASES; CARCINOID-TUMORS; DEPOT OCTREOTIDE; BEVACIZUMAB; PERFUSION; FLUOROURACIL; STREPTOZOCIN; TEMOZOLOMIDE;
D O I
10.1097/MPA.0000000000001258
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objectives Therapies for patients with advanced well-differentiated pancreatic neuroendocrine tumors (pNETs) are insufficient, with patients succumbing to disease despite recent treatment advances. Ziv-aflibercept is a fusion protein of portions of the vascular endothelial growth factor (VEGF) receptors 1 and 2, fused to the Fc portion of immunoglobulin G1, forming a VEGF trap. Perfusion computed tomography (CT) has previously defined hyperperfused neuroendocrine tumors, potentially predicting antiangiogenic benefit. Methods We performed a single-arm open-label study, using the Simon optimal 2-stage design, of 6 mg/kg ziv-aflibercept in patients with advanced pNETs. The primary end point was objective radiographic response, with a hierarchically tested co-primary end point of response prediction by baseline hyperperfusion, defined as blood volume greater than 5.25 mL/100 g and permeability surface area product greater than 25 mL/min per 100 g. Results Between July 3, 2014, and September 28, 2016, 21 patients were treated. Two patients (9.5%; 95% confidence interval, 1.1%-30.4%) demonstrated objective response, satisfying criteria to open the second stage, but the study was terminated for accrual. Perfusion CT could not be confirmed to predict radiographic response. Toxicities include 1 grade 5 gastrointestinal hemorrhage and 5 incidents of proteinuria requiring treatment discontinuation. Conclusions Responses with ziv-aflibercept were consistent with other VEGF inhibitors in pNET, but perfusion CT could not be confirmed to predict outcome.
引用
收藏
页码:381 / 386
页数:6
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