Lessons learned: Pazopanib 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). 68Ga-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.
经验教训
• 帕唑帕尼治疗转移性腺泡状软组织肉瘤的疗效一般。
• 临床结果与既往使用抗血管生成药物的研究结果相差无几。
• 未来需要较大样本的前瞻性研究评估帕唑帕尼在腺泡状软组织肉瘤中疗效,以验证结果。
摘要
背景。腺泡状软组织肉瘤 (ASPS) 是一种罕见的间充质恶性肿瘤,其特点是易位不平衡,t(X;17)(p11.2;q25),进而造成 ASPSCR1 到 TFE3 转录因子的融合。由于造成血管生成相关转录的上调,抗血管生成药物已被用于 ASPS 患者。
方法。这项开放标签、单臂、多中心且由研究员发起的 II 期试验旨在评估转移性 ASPS 患者帕唑帕尼800 mg每天服用一次的疗效和安全性。主要疗效指标是研究员评估的总缓解率 (ORR),次要疗效指标是毒性、无进展生存期 (PFS) 和总生存期 (OS)。利用 NanoString 平台对68Ga‐RGD (Arg ‐ Gly ‐ Asp) 正电子发射断层扫描 (PET) 和基因表达谱进行了生物标志物分析。
结果。2013 年 12 月至 2014 年 11 月间,共有 6 名经组织学证实的转移性 ASPS 患者参与研究。这 6 名患者中,1 人部分缓解 (PR) (ORR 16.7%), 另 5 人病情稳定 (SD)。平均随访时间为 33 个月(范围是 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],未达到中位 OS。未发现严重毒性,只有一位患者出现 3 级腹泻。
结论。帕唑帕尼对转移性 ASPS 患者表现出一般的抗肿瘤活性和可控制的毒性。
Trial registration: ClinicalTrials.gov NCT02113826.
© AlphaMed Press; the data published online to support this summary is the property of the authors.