Summit Cancer Centers, Post Falls, Idaho.
Sarcoma Oncology Center, Santa Monica, California.
Cancer. 2017 Dec 1;123(23):4640-4647. doi: 10.1002/cncr.30926. Epub 2017 Aug 18.
This phase 2, single-arm, multicenter study was designed to determine the treatment activity and safety of single-agent pazopanib in patients with unresectable or metastatic liposarcoma.
Eligible patients had high-grade or intermediate-grade liposarcoma with measurable tumors that were unresectable or metastatic, documented disease progression, and had received any number of prior treatments, excluding previous treatment with a vascular endothelial growth factor inhibitor or a tyrosine kinase inhibitor. Patients received oral pazopanib 800 mg once daily for 28-day cycles. Tumor response was evaluated by local radiology assessments every 3 cycles. The primary endpoint was the progression-free rate (PFR) at 12 weeks (PFR12).
Forty-one patients were enrolled. The PFR12 was 68.3% (95% confidence interval [CI], 51.9%-81.9%), which was significantly greater than the null hypothesis value of 40% (P = .0002). At 24 weeks, 39% of patients (95% CI, 24.2%-55.5%) remained progression free, and 44% experienced tumor control (partial response or stable disease). The median progression-free survival was 4.4 months (95% CI, 3.2-6.5 months), and the median overall survival was 12.6 months (95% CI, 8.5-16.2 months). The most common adverse events overall were nausea (39%), hypertension (36.6%), diarrhea (34.1%), and fatigue (29.3%), which were typically less than grade 3. There were 5 deaths on study (12.2%), 3 of which were from possible complications of therapy.
The current study provides evidence of potential activity of pazopanib in the liposarcoma subset of patients with soft tissue sarcoma that was specifically excluded from the phase 3 PALETTE trial of other soft tissue sarcoma types. Cancer 2017;123:4640-4647. © 2017 American Cancer Society.
本 2 期、单臂、多中心研究旨在确定单药帕唑帕尼在不可切除或转移性脂肪肉瘤患者中的治疗活性和安全性。
符合条件的患者患有高级或中级脂肪肉瘤，有可测量的肿瘤，无法切除或转移，有记录的疾病进展，并且接受了任何数量的先前治疗，不包括先前使用血管内皮生长因子抑制剂或酪氨酸激酶抑制剂的治疗。患者接受口服帕唑帕尼 800mg，每天一次，每 28 天为一个周期。每 3 个周期进行一次局部放射学评估以评估肿瘤反应。主要终点是 12 周时的无进展率（PFR12）。
共纳入 41 例患者。PFR12 为 68.3%（95%置信区间[CI]，51.9%-81.9%），显著高于 40%的零假设值（P=.0002）。24 周时，39%的患者（95%CI，24.2%-55.5%）无进展，44%的患者肿瘤得到控制（部分缓解或疾病稳定）。中位无进展生存期为 4.4 个月（95%CI，3.2-6.5 个月），中位总生存期为 12.6 个月（95%CI，8.5-16.2 个月）。总体最常见的不良事件是恶心（39%）、高血压（36.6%）、腹泻（34.1%）和疲劳（29.3%），通常低于 3 级。研究中有 5 例死亡（12.2%），其中 3 例可能与治疗相关并发症有关。
目前的研究提供了帕唑帕尼在软组织肉瘤中脂肪肉瘤亚组患者中具有潜在活性的证据，这些患者是软组织肉瘤的 3 期 PALETTE 试验中其他软组织肉瘤类型所特别排除的。癌症 2017；123：4640-4647。©2017 美国癌症协会。
