[F]氟西拉肽正电子发射断层扫描作为铂耐药/难治性卵巢癌中帕唑帕尼和紫杉醇联合治疗反应的生物标志物。
[F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer.
作者信息
Sharma Rohini, Valls Pablo Oriol, Inglese Marianna, Dubash Suraiya, Chen Michelle, Gabra Hani, Montes Ana, Challapalli Amarnath, Arshad Mubarik, Tharakan George, Chambers Ed, Cole Tom, Lozano-Kuehne Jingky P, Barwick Tara D, Aboagye Eric O
机构信息
Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0HS, UK.
Department of Computer, Control and Management Engineering Antonio Ruberti, University of Rome "La Sapienza", Rome, Italy.
出版信息
Eur J Nucl Med Mol Imaging. 2020 May;47(5):1239-1251. doi: 10.1007/s00259-019-04532-z. Epub 2019 Nov 21.
BACKGROUND
Angiogenesis is a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum-resistant/refractory ovarian cancer. Integrins αβ and αβ are both upregulated in tumor-associated vasculature. [F]Fluciclatide is a novel PET tracer that has high affinity for integrins αβ, and was used to assess the anti-angiogenic effect of pazopanib.
PATIENTS AND METHODS
We conducted an open-label, phase Ib study in patients with platinum-resistant/refractory ovarian cancer. Patients received 1 week of single-agent pazopanib (800 mg daily) followed by combination therapy with weekly paclitaxel (80 mg/m). Following completion of 18 weeks of combination therapy, patients continued with single-agent pazopanib until disease progression. Dynamic [F]fluciclatide-PET imaging was conducted at baseline and after 1 week of pazopanib. Response (RECIST 1.1), toxicities, and survival outcomes were recorded. Circulating markers of angiogenesis were assessed with therapy.
RESULTS
Fourteen patients were included in the intention-to-treat analysis. Complete and partial responses were seen in seven patients (54%). Median progression-free survival (PFS) was 10.63 months, and overall survival (OS) was 18.5 months. Baseline [F]fluciclatide uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and fibroblast growth factor (FGF) were predictive of greater reduction in SUV following pazopanib. Kinetic modeling of PET data indicated a reduction in K and K following pazopanib indicating reduced radioligand delivery and retention.
CONCLUSIONS
Combination therapy followed by maintenance pazopanib is effective and tolerable in platinum-resistant/refractory ovarian cancer. [F]Fluciclatide-PET uptake parameters predict clinical outcome with pazopanib therapy indicating an anti-angiogenic response.
背景
血管生成是卵巢癌铂耐药的驱动因素。我们评估了帕唑帕尼与紫杉醇联合用药后维持使用帕唑帕尼对铂耐药/难治性卵巢癌患者的疗效。整合素αβ和αβ在肿瘤相关脉管系统中均上调。[F]氟西拉肽是一种对整合素αβ具有高亲和力的新型正电子发射断层显像（PET）示踪剂，用于评估帕唑帕尼的抗血管生成作用。
患者与方法
我们对铂耐药/难治性卵巢癌患者进行了一项开放标签的Ib期研究。患者先接受1周的单药帕唑帕尼治疗（每日800毫克），随后接受每周紫杉醇（8毫克/平方米）的联合治疗。联合治疗18周结束后，患者继续接受单药帕唑帕尼治疗直至疾病进展。在基线期和帕唑帕尼治疗1周后进行动态[F]氟西拉肽-PET成像。记录疗效（实体瘤疗效评价标准1.1版）、毒性和生存结果。治疗期间评估血管生成的循环标志物。
结果
14例患者纳入意向性分析。7例患者（54%）出现完全缓解和部分缓解。中位无进展生存期（PFS）为10.63个月，总生存期（OS）为1个月。基线[F]氟西拉肽摄取可预测长PFS。基线循环血管生成素和成纤维细胞生长因子（FGF）升高可预测帕唑帕尼治疗后标准化摄取值（SUV）降低幅度更大。PET数据的动力学模型表明，帕唑帕尼治疗后K和K降低，表明放射性配体递送和滞留减少。
结论
联合治疗后维持使用帕唑帕尼对铂耐药/难治性卵巢癌有效且耐受性良好。[F]氟西拉肽-PET摄取参数可预测帕唑帕尼治疗的临床结果，表明存在抗血管生成反应。
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