A Phase II Trial of Pazopanib in Patients with Metastatic Alveolar Soft Part Sarcoma
A Phase II Trial of Pazopanib in Patients with Metastatic Alveolar Soft Part Sarcoma
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DOI：
10.1634/theoncologist.2018-0464
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发表时间：
2019-01-01
期刊：
影响因子：
5.8
通讯作者：
Heo, Dae Seog
中科院分区：
文献类型：
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作者：
Kim, Miso;Kim, Tae Min;Heo, Dae Seog
帕唑帕尼在转移性肺泡软组织肉瘤中显示出适度的疗效。临床结果与先前使用抗血管生成药物的研究相当。进一步的前瞻性研究评估帕唑帕尼治疗肺泡软组织肉瘤的益处，样本量更大，以验证结果。肺泡软组织肉瘤（Alveolar soft part sarcoma, asp）是一种罕见的间充质恶性肿瘤，其特征是不平衡易位，t(X;17)(p11.2;q25)，导致ASPSCR1与TFE3转录因子融合。由于这导致血管生成相关转录物的上调，抗血管生成药物已被用于ASPS患者。该开放标签、单臂、多中心、研究者启动的II期试验旨在评估pazopanib 800 mg / d 1次治疗转移性asp患者的有效性和安全性。主要终点是研究者评估的总缓解率（ORR），次要终点是毒性、无进展生存期（PFS）和总生存期（OS）。采用Ga-68-RGD （Arg-Gly-Asp）正电子发射断层扫描（PET）和NanoString平台进行基因表达谱分析。结果2013年12月至2014年11月，6例组织学证实的转移性ASPS患者入组。6例患者中，1例达到部分缓解（PR） （ORR 16.7%）， 5例病情稳定（SD）。中位随访时间为33个月（18.7-39.3个月），中位PFS为5.5个月（95%置信区间[CI] 3.4-7.6个月），中位OS未达到。除1例3级腹泻外，无严重毒性反应。结论Pazopanib对转移性ASPS患者具有适度的抗肿瘤活性和可控的毒性。
Lessons LearnedPazopanib shows a modest efficacy in metastatic alveolar soft part sarcoma. Clinical outcomes were comparable to those in previous studies using antiangiogenic drugs. Further prospective studies evaluating the benefit of pazopanib in alveolar soft part sarcoma with a larger sample are warranted to validate results. Background Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignant tumor characterized by an unbalanced translocation, t(X;17)(p11.2;q25), which leads to the fusion of ASPSCR1 to the TFE3 transcription factor. Because this results in the upregulation of angiogenesis-related transcripts, antiangiogenic drugs have been used in ASPS patients. Methods This open-label, single-arm, multicenter, investigator-initiated phase II trial was designed to evaluate efficacy and safety of pazopanib 800 mg once daily in patients with metastatic ASPS. The primary endpoint was investigator-assessed overall response rate (ORR), and secondary endpoints were toxicity, progression-free survival (PFS), and overall survival (OS). Ga-68-RGD (Arg-Gly-Asp) positron emission tomography (PET) scan and gene expression profiling using NanoString platform were performed for biomarker analysis. Results Six patients with histologically confirmed metastatic ASPS were enrolled between December 2013 and November 2014. Among six patients, one achieved a partial response (PR) (ORR 16.7%) and five patients showed stable disease (SD). With a median follow-up of 33 months (range 18.7-39.3 months), median PFS was 5.5 months (95% confidence interval [CI] 3.4-7.6 months), and median OS was not reached. There were no severe toxicities except one patient with grade 3 diarrhea. Conclusion Pazopanib showed modest antitumor activity with manageable toxicities for patients with metastatic ASPS.