索拉非尼治疗晚期血管肉瘤患者：来自法国肉瘤集团（GSF/GETO）的 II 期试验。
Sorafenib for patients with advanced angiosarcoma: a phase II Trial from the French Sarcoma Group (GSF/GETO).
机构信息
Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
出版信息
Oncologist. 2012;17(2):260-6. doi: 10.1634/theoncologist.2011-0237. Epub 2012 Jan 27.
BACKGROUND
Angiosarcomas account for <2% of all soft tissue sarcomas. This subtype is one of the most aggressive forms of soft tissue sarcoma. The prognosis for angiosarcoma patients in the advanced phase remains poor with current cytotoxic agents (progression-free survival [PFS] time of ∼4 months and overall survival [OS] time of ∼8 months). We investigated the antitumor activity of sorafenib in patients with metastatic or advanced angiosarcomas in a phase II trial.
METHODS
We conducted a stratified phase II trial. The primary endpoint was the progression-free rate (PFR) at 9 months according to the Response Evaluation Criteria in Solid Tumors. A two-stage design (optimal Simon design) was used. Patients received sorafenib (400 mg twice daily) for 9 months until unacceptable toxicity or tumor progression. Central pathological and radiological reviews were performed. Data on stratum A (superficial angiosarcoma) and stratum B (visceral angiosarcoma) are currently available. This trial is registered with ClinicalTrials.gov (identifier, NCT00874874).
FINDINGS
Strata A and B recruited 26 and 15 patients, respectively. The median age was 63 years (range, 31-82 years), with 17 male and 24 female patients. Fourteen cases arose in irradiated fields. Thirty patients (73.0%) had been pretreated with conventional chemotherapy. No unexpected toxicity occurred. The PFR at 9 months was 3.8% in stratum A and 0.0% in stratum B. The median PFS times were 1.8 months and 3.8 months, respectively, whereas the median OS times were 12.0 months and 9.0 months, respectively. No responses were observed in chemotherapy-naïve patients, whereas a 40% tumor control rate and 23% response rate were observed in the pretreated population. In this cohort, no activating mutation of the KDR gene (exons 15, 16, 24) was detected.
INTERPRETATION
Sorafenib showed limited antitumor activity in pretreated patients only, for both visceral and superficial angiosarcoma, but tumor control was of short duration.
背景
血管肉瘤约占所有软组织肉瘤的<2%。这种亚型是软组织肉瘤中最具侵袭性的形式之一。目前，对于晚期血管肉瘤患者，使用细胞毒性药物的预后仍然较差（无进展生存期[PFS]约为 4 个月，总生存期[OS]约为 8 个月）。我们在一项 II 期试验中研究了索拉非尼在转移性或晚期血管肉瘤患者中的抗肿瘤活性。
方法
我们进行了分层 II 期试验。主要终点是根据实体瘤反应评估标准（RECIST）评估的 9 个月时的无进展率（PFR）。采用两阶段设计（最优西蒙设计）。患者接受索拉非尼（每天两次，每次 400mg）治疗 9 个月，直到出现不可接受的毒性或肿瘤进展。进行了中央病理学和影像学审查。目前可提供关于 A 层（浅表血管肉瘤）和 B 层（内脏血管肉瘤）的数据。这项试验在 ClinicalTrials.gov 上注册（标识符：NCT00874874）。
结果
A 层和 B 层分别招募了 26 名和 15 名患者。中位年龄为 63 岁（范围：31-82 岁），男性 17 名，女性 24 名。14 例发生于放疗野内。30 名患者（73.0%）曾接受过常规化疗。未发生意外毒性。A 层 9 个月时的 PFR 为 3.8%，B 层为 0.0%。中位 PFS 时间分别为 1.8 个月和 3.8 个月，中位 OS 时间分别为 12.0 个月和 9.0 个月。化疗初治患者未观察到应答，而在预处理人群中观察到 40%的肿瘤控制率和 23%的应答率。在该队列中，未检测到 KDR 基因（外显子 15、16、24）的激活突变。
解释
索拉非尼仅在预处理患者中对内脏和浅表血管肉瘤显示出有限的抗肿瘤活性，但肿瘤控制的持续时间很短。
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