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Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2)
Liver Cancer ( IF 11.6 ) Pub Date : 2021-07-12 , DOI: 10.1159/000516605
Masatoshi Kudo , Richard S. Finn , Manabu Morimoto , Kun-Ming Rau , Masafumi Ikeda , Chia-Jui Yen , Peter R. Galle , Josep M. Llovet , Bruno Daniele , Ho Yeong Lim , David W. McIlwain , Reigetsu Yoshikawa , Kenichi Nakamura , Kun Liang , Chunxiao Wang , Paolo Abada , Ryan C. Widau , Andrew X. Zhu

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:


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
更新日期:2021-07-12
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