A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium
A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium
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DOI：
10.1634/theoncologist.2010-0081
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发表时间：
2010-08-01
期刊：
影响因子：
5.8
通讯作者：
Leighl, Natasha B.
中科院分区：
文献类型：
--
作者：
Taylor, Sara K.;Chia, Stephen;Leighl, Natasha B.
目的。血管生成是乳腺癌生长和发展的重要标志。帕佐帕尼是一种口服血管内皮生长因子受体、血小板衍生生长因子受体和试剂盒的小分子抑制剂，对一系列实体肿瘤具有活性。我们评估单药帕佐帕尼在复发或转移性乳腺癌(MBC)中的活性。复发的乳腺癌或MBC患者，在接受最多两个先前的化疗方案治疗后，有资格接受帕唑帕尼，每天800毫克，直到病情恶化。主要终点是根据实体瘤的反应评估标准测量的客观应答率。次要终点包括进展时间、稳定发病率和毒性。采用两阶段设计，18名患者中有3名患者需要确认应答才能进入第二阶段。20名可评价患者接受治疗，中位年龄56岁；70%雌激素受体阳性，均为人表皮生长因子受体2阴性。大多数人之前曾接受过一到两次化疗。1例(5%)患者部分缓解，11例(55%)病情稳定(SD)[4例(20%)SD>；=6个月]，7例(35%)病情进展最佳。1例(5%)不可评价。中位进展时间为5.3个月。帕佐帕尼除3例(14%)出现3~4级转氨炎、高血压和中性粒细胞减少症，1例(5%)发生3级胃肠道出血外，未出现明显的严重毒性反应。帕佐帕尼在晚期乳腺癌中提供了疾病稳定性。在这种情况下，所看到的活性与其他抗血管生成剂的活性相当。帕佐帕尼可能会对未来乳腺癌的研究感兴趣，包括与其他全身药物的联合应用。《肿瘤学家》2010；15：810-818
Purpose. Angiogenesis is an important hallmark of breast cancer growth and progression. Pazopanib, an oral small molecule inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and KIT, has activity across a range of solid tumors. We evaluated the activity of single-agent pazopanib in recurrent or metastatic breast cancer (MBC).Patients and Methods. Patients with recurrent breast cancer or MBC, treated with up to two prior lines of chemotherapy, were eligible to receive pazopanib, 800 mg daily until progression. The primary endpoint was the objective response rate as measured by Response Evaluation Criteria in Solid Tumors. Secondary endpoints included time to progression, the stable disease rate, and toxicity. Using a two-stage design, confirmed response in three of 18 patients was required to proceed to stage 2.Results. Twenty evaluable patients were treated, with a median age of 56 years; 70% were estrogen receptor positive, all were human epidermal growth factor receptor 2 negative. The majority had one or two prior lines of chemotherapy. One patient (5%) had a partial response, 11 (55%) had stable disease (SD) [four (20%) with SD >= 6 months], and seven (35%) had progressive disease as their best response. One (5%) was not evaluable. The median time to progression was 5.3 months. Pazopanib did not cause significant severe toxicity aside from grade 3-4 transaminitis, hypertension, and neutropenia in three patients each (14% each) and grade 3 gastrointestinal hemorrhage in one patient (5%).Conclusion. Pazopanib provides disease stability in advanced breast cancer. The activity seen is comparable with that of other antiangiogenic agents in this setting. Pazopanib may be of interest for future studies in breast cancer, including in combination with other systemic agents. The Oncologist 2010;15:810-818