Background: Intermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. Methods: A pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0–1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score. Results: Baseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546–1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23–0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59–0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages. Conclusions: Ramucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.
Liver Cancer

中文翻译：

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Ramucirumab 用于治疗中期肝细胞癌和甲胎蛋白升高的患者：两项 3 期研究（REACH 和 REACH-2）的汇总结果


背景：根据巴塞罗那临床肝癌 (BCLC) B 期定义，中期肝细胞癌 (HCC) 在肝功能和肿瘤负荷方面存在异质性。 REACH 和 REACH-2 研究了雷莫芦单抗在既往索拉非尼治疗后的 HCC 患者中的应用，其中 REACH-2 仅招募基线甲胎蛋白 (AFP) ≥400 ng/mL 的患者。对 BCLC 分期的结果进行了探索性分析。方法：对来自 REACH (AFP ≥ 400 ng/mL) 和 REACH-2 的独立患者数据（按研究分层）进行汇总荟萃分析。所有患者均具有 Child-Pugh A 级、东部肿瘤合作组表现状态 0-1、既往索拉非尼治疗以及 HCC BCLC B 期（难治性/不适合局部治疗）或 BCLC C 期。患者被随机分配至雷莫芦单抗 8 mg/组每 2 周服用 1 公斤或安慰剂。中位总生存期（OS）和无进展生存期通过 Kaplan-Meier 方法估计。采用Cox比例风险模型评估BCLC B期和C期的治疗效果；通过多变量 Cox 比例风险模型评估 BCLC 分期的 OS 预后。根据实体瘤v1.1中的反应评估来评估肿瘤反应。用白蛋白-胆红素评分评估肝功能。结果：每个 BCLC 阶段的治疗组之间的基线特征总体上是平衡的。 BCLC 分期趋势为 OS 的独立预后因素（B 与 C；风险比 [HR] 0.756 [95% CI 0.546–1.046]）。在整个 BCLC 阶段中，观察到雷莫芦单抗与安慰剂相比具有一致的治疗益处。雷莫芦单抗与安慰剂相比，中位 OS 分别为 13.7 个月和 8.2 个月； HR (95%)：0.43 (0.23–0.83) 和 7.7 与 4。8个月； HR (95%)：BCLC B 期和 C 期分别为 0.72 (0.59–0.89)。不良事件（AE）与两项研究的观察结果一致；高血压是最常见的 ≥3 级 AE。在整个研究过程中，肝功能得到保留，并且在两个 BCLC 阶段的治疗组之间肝功能相似。结论：无论 BCLC 分期如何，雷莫芦单抗均可提供更好的生存获益，并且耐受性良好，且治疗期间不会损害肝功能。
 肝癌