Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial
Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial
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DOI：
10.1016/j.jhep.2016.01.012
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发表时间：
2016-05-01
影响因子：
25.7
通讯作者：
Bruix, Jordi
中科院分区：
文献类型：
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作者：
Lencioni, Riccardo;Llovet, Josep M.;Bruix, Jordi
背景与目的：阿霉素洗脱微球肝动脉化疗栓塞术(DC Bead(R)；DEB-TACE)是治疗巴塞罗那临床B期肝细胞癌的有效方法。多激酶抑制剂索拉非尼可提高晚期肝癌患者的总存活率(OS)和肿瘤进展时间(TIP)。这项探索性II期试验测试了DEB-TACE联合索拉非尼治疗中期肝癌的疗效和安全性。方法：将无大血管侵犯(MVI)或肝外扩散(EHS)的中期多结节肝癌患者随机分为DEB-TACE(阿霉素150 mg+索拉非尼400 mg，每日2次)或安慰剂(安慰剂)。通过中心盲法评价，主要终点为TTP。次要终点包括达到MVI/EHS的时间、OS、在实体肿瘤中使用改进的反应评估标准的总有效率(ORR)、疾病控制率(DCR)、不能进展的时间(TTUP)和安全性。结果：在随机选择的307名患者中，154名服用索拉非尼，153名服用安慰剂。接受索拉非尼联合化疗栓塞术或安慰剂联合化疗栓塞术的受试者的中位TIP相似(分别为169天和166天；风险比(HR)0.797，p=0.072)。MVI/EHS(HR 0.621，p=0.076)和OS(HR 0.898，p=0.29)的中位时间尚未达到。索拉非尼组和安慰剂组患者基线后扫描的ORR5分别为55.9%和41.3%，DCRS分别为89.2%和76.1%。服用索拉非尼的患者TTUP低于服用安慰剂的患者(HR为1.586；95%可信区间为1.200-2.096；中位数为95天，而安慰剂为224天)。未观察到与索拉非尼有关的意外不良事件。结论：索拉非尼联合DEB-TACE在技术上是可行的，但与单独使用DEB-TACE相比，联合应用并不能在临床上改善TTP。(C)2016年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background & Aims: Transarterial chemoembolization with doxorubicin-eluting beads (DC Bead (R); DEB-TACE) is effective in patients with Barcelona clinic liver cancer stage B hepatocellular carcinoma (HCC). The multikinase inhibitor sorafenib enhances overall survival (OS) and time-to-tumor progression (TIP) in patients with advanced HCC. This exploratory phase II trial tested the efficacy and safety of DEB-TACE plus sorafenib in patients with intermediate stage HCC.Methods: Patients with intermediate stage multinodular HCC without macrovascular invasion (MVI) or extrahepatic spread (EHS) were randomized 1:1 to DEB-TACE (150 mg doxorubicin) plus sorafenib 400 mg twice daily or placebo. The primary endpoint was TTP by blinded central review. Secondary endpoints included time to MVI/EHS, OS, overall response rate (ORR) using modified response evaluation criteria in solid tumors, disease control rate (DCR), time to unTACEable progression (TTUP), and safety.Results: Of 307 patients randomized, 154 received sorafenib and 153 received placebo. Median TIP for subjects receiving sorafenib plus DEB-TACE or placebo plus DEB-TACE was similar (169 vs. 166 days, respectively; hazard ratio (HR) 0.797, p = 0.072). Median time to MVI/EHS (HR 0.621, p = 0.076) and OS (HR 0.898, p = 0.29) had not been reached. The ORR5 for patients in the sorafenib and placebo groups with post-baseline scans were 55.9% and 41.3%, respectively, and the DCRs were 89.2% and 76.1%, respectively. TTUP was lower with sorafenib than with placebo (HR 1.586; 95% confidence intervals, 1.200-2.096; median 95 vs. 224 days). No unexpected adverse events related to sorafenib were observed.Conclusion: Sorafenib plus DEB-TACE was technically feasible, but the combination did not improve TTP in a clinically meaningful manner compared with DEB-TACE alone. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.