Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib: Patient-focused outcome results from the randomised phase III REACH study
Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib: Patient-focused outcome results from the randomised phase III REACH study
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DOI：
10.1016/j.ejca.2017.05.001
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发表时间：
2017-08-01
影响因子：
8.4
通讯作者：
Zhu, Andrew X.
中科院分区：
文献类型：
--
作者：
Chau, Ian;Peck-Radosavljevic, Markus;Zhu, Andrew X.
目的：报告以生活质量（QoL）和表现状态（PS）衡量的以患者为中心的结果，REACH是一项III期安慰剂对照随机研究，评估ramucirumab在先前接受索拉非尼治疗的晚期肝细胞癌（HCC）患者中的应用。方法：符合条件的晚期HCC患者，Child-Pugh A， PS 0或1，既往使用索拉非尼。患者在2周周期的第1天接受ramucirumab （8mg /kg）或安慰剂（1:1）治疗。基线时采用FACT肝胆症状指数(FHSI)-8和EuroQoL （EQ-5D）评估生活质量；周期4、10和16；治疗结束。在基线、每个周期和治疗结束时评估PS。FHSI-8恶化定义为>= 3点较基线下降，PS恶化定义为>= 2点变化。对基线血清甲胎蛋白(AFP) >= 400 ng/mL的患者进行意向治疗和预先指定的亚组评估。结果：565例患者随机分为ramucirumab组和安慰剂组。各组间FHSI和EQ-5D的依从性较高且相似。在ITT人群中，ramucirumab和安慰剂组的FHSI-8、EQ-5D和PS的恶化相似。在基线AFP >= 400 ng/mL的患者中，与安慰剂相比，ramucirumab在治疗结束时显著减少了FHSI-8的恶化（P = 0.0381），并且有利于ramucirumab的FHSI-8 （HR 0.690; P = 0.054）和PS （HR 0.642; P = 0.057）的症状恶化有延迟的趋势。结论：我们报告了晚期HCC接受全身治疗患者的生活质量和症状负担的最全面的数据集之一。Ramucirumab与生活质量无恶化相关。在基线AFP >= 400 ng/mL的患者中，在接受ramucirumab治疗的患者中观察到的显着生存获益与以患者为中心的结局获益趋势相结合。临床试验注册：NCT01140347。(C) 2017 Elsevier Ltd.版权所有。
Purpose: To report patient-focused outcomes as measured by quality of life (QoL) and performance status (PS) in REACH, a phase III placebo-controlled randomised study, assessing ramucirumab in advanced hepatocellular carcinoma (HCC) patients who received prior sorafenib.Methods: Eligible patients had advanced HCC, Child-Pugh A, PS 0 or 1 and prior sorafenib. Patients received ramucirumab (8 mg/kg) or placebo (1:1) on day 1 of a 2-week cycle. QoL was assessed by FACT Hepatobiliary Symptom Index (FHSI)-8 and EuroQoL (EQ-5D) at baseline; cycles 4, 10, and 16; and end of treatment. PS was assessed at baseline, each cycle, and end of treatment. Deterioration in FHSI-8 was defined as a >= 3-point decrease from baseline and PS deterioration was defined as a change of >= 2. Both intention-to-treat and pre-specified subgroup of patients with baseline serum alpha-fetoprotein (AFP) >= 400 ng/mL were assessed.Results: There were 565 patients randomised to ramucirumab and placebo. Compliance with FHSI and EQ-5D was high and similar between groups. In the ITT population, deterioration in FHSI-8, EQ-5D, and PS was similar between ramucirumab and placebo. In patients with baseline AFP >= 400 ng/mL, ramucirumab significantly reduced deterioration in FHSI-8 at the end of treatment compared with placebo (P = 0.0381), and there was a trend towards a delay in the deterioration of symptoms in FHSI-8 (HR 0.690; P = 0.054) and PS (HR 0.642; P = 0.057) in favour of ramucirumab.Conclusions: We report one of the most comprehensive data sets of QoL and symptom burden in patients undergoing systemic therapy for advanced HCC. Ramucirumab was associated with no worsening of QoL. In patients with baseline AFP >= 400 ng/mL, the significant survival benefit observed in patients treated with ramucirumab was coupled with a trend in patientfocused outcome benefits. Clinical trial registration: NCT01140347. (C) 2017 Elsevier Ltd. All rights reserved.