Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK; University of Manchester, Division of Cancer Sciences, Manchester, M20 4BX, UK.
Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK; University of Amsterdam, the Netherlands.
Eur J Cancer. 2018 Dec;105:1-9. doi: 10.1016/j.ejca.2018.09.031. Epub 2018 Oct 29.
Sorafenib has demonstrated survival benefit in first-line treatment of advanced hepatocellular carcinoma (HCC); utility of sorafenib in patients with advanced HCC and Child-Pugh B (CP-B) liver function remains a subject of debate.
A systematic review identified studies using first-line sorafenib in patients with advanced HCC and CP-A/B liver function. Meta-regression analysis comprising linear regression was conducted to explore the association between the baseline factors and overall survival (OS). Differences between efficacy/safety and tolerability parameters were explored using meta-analysis.
Thirty studies (12 Asian) comprising 8678 patients (August 2002 - September 2012) were included (four randomised controlled trials, 26 cohort studies). Median age was 61 years and 83% were men. Hepatitis B/C status was positive in 35%/22%, respectively. The CP status was available for 8577 patients (99%); CP-A, 79% and CP-B, 19%. Median OS on sorafenib for entire cohort was 7.2 months; 8.8 months in CP-A and 4.6 months in CP-B. Multivariable meta-regression analysis showed significant negative association between OS and proportion of patients with the Eastern Cooperative Oncology Group performance status 2 (P = 0.04) and CP-B liver function (P = 0.001). Among four studies reporting multivariable comparison of the CP status, CP-B was associated with significantly worse OS (P < 0.001). There were no differences in the response rate to sorafenib between patients with CP-A (4.6%) and CP-B (4.2%) liver function. Safety and tolerability were similar; 35% of patients with CP-A/B liver function developed grade III/IV adverse events (P = 0.7). Meta-regression analysis showed similar rates of treatment discontinuation without progression (P = 0.31) and treatment-related death (P = 0.94) in patients with CP-B liver function.
CP-B liver function (versus CP-A) is associated with worse OS (but the similar response rate, safety and tolerability of first-line sorafenib, is unlikely to be clinically meaningful).
索拉非尼在晚期肝细胞癌（HCC）的一线治疗中已显示出生存获益；索拉非尼在肝功能为 Child-Pugh B（CP-B）的晚期 HCC 患者中的应用仍然存在争议。
系统评价确定了使用一线索拉非尼治疗晚期 HCC 伴 CP-A/B 肝功能的研究。采用线性回归的荟萃回归分析来探讨基线因素与总生存期（OS）之间的关系。使用荟萃分析探讨疗效/安全性和耐受性参数之间的差异。
共纳入 30 项研究（12 项来自亚洲），包括 8678 例患者（2002 年 8 月至 2012 年 9 月）（4 项随机对照试验，26 项队列研究）。中位年龄为 61 岁，83%为男性。乙型肝炎/丙型肝炎阳性率分别为 35%/22%。8577 例患者（99%）的 CP 状态可用；CP-A 占 79%，CP-B 占 19%。整个队列的索拉非尼中位 OS 为 7.2 个月；CP-A 为 8.8 个月，CP-B 为 4.6 个月。多变量荟萃回归分析显示，OS 与东部肿瘤协作组体力状态 2（P=0.04）和 CP-B 肝功能（P=0.001）的患者比例之间存在显著的负相关。四项报告 CP 状态多变量比较的研究中，CP-B 与明显较差的 OS 相关（P<0.001）。CP-A（4.6%）和 CP-B（4.2%）肝功能患者对索拉非尼的反应率无差异。安全性和耐受性相似；CP-A/B 肝功能患者中有 35%发生 3/4 级不良事件（P=0.7）。荟萃回归分析显示，CP-B 肝功能患者无进展性疾病停药率（P=0.31）和治疗相关死亡率（P=0.94）相似。
CP-B 肝功能（与 CP-A 相比）与较差的 OS 相关（但一线索拉非尼的反应率、安全性和耐受性相似，不太可能具有临床意义）。
