来那度胺作为晚期肝细胞癌的二线治疗：探索生物标志物治

StephenW

Lenalidomide as second-line therapy for advanced hepatocellular carcinoma: exploration of biomarkers for treatment efficacy

    Y.-Y. Shao1,2,3, B.-B. Chen4, D.-L. Ou1,2, Z.-Z. Lin3,5, C.-H. Hsu1,2,3, M.-J. Wang3, A.-L. Cheng1,2,3,5 andC. Hsu1,2,3,*

Version of Record online: 17 AUG 2017

DOI: 10.1111/apt.14270


    1    Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan
    2    National Taiwan University Cancer Center, Taipei, Taiwan
    3    Departments of Oncology, National Taiwan University Hospital, Taipei, Taiwan
    4    Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
    5    Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Email: C. Hsu ([email protected])

* Correspondence
Dr. C. Hsu, Graduate Institute of Oncology, National Taiwan University, College of Medicine, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Email: [email protected]

   
Abstract
Background

Lenalidomide has immunomodulatory and anti-angiogenic effects and showed moderate anti-tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC)
Aim

To explore potential biomarkers of lenalidomide efficacy as second-line therapy for HCC.
Methods

Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child-Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1-21 every 4 weeks. The primary endpoint was 6 month progression-free survival rate. Early α-fetoprotein response was defined as a > 20% decline of α-fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast-enhanced magnetic resonance imaging, was defined as a > 40% decline in Ktrans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed.
Results

Fifty-five patients were enrolled. The response rate was 13%, and the disease-control rate was 53%. The 6 month progression-free survival rate was 9.1%. The median progression-free and overall survival was 1.8 months and 8.9 months respectively. Early α-fetoprotein response was significantly associated with higher disease-control rate (76% vs 22%, P = .001) and longer progression-free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre-treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression-free survival (P < .001) and overall survival (P = .042).
Conclusions

Lenalidomide exhibited moderate activity as second-line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804).

StephenW

来那度胺作为晚期肝细胞癌的二线治疗：探索生物标志物治疗功效

    Y.-Y.邵1,2,3，B.-B. Chen4，D.-L. Ou1,2，Z.-Z. Lin3,5，C.-H. Hsu1,2,3，M.-J. Wang3，A.-L.程1,2,3,5和C. Hsu1,2,3，*

在线记录版本：17 AUG 2017

DOI：10.1111 / apt.14270


    1台湾台北大学医学院肿瘤研究所
    2台湾台北大学癌症中心，台北
    台湾台北大学附属医院肿瘤科3部
    4台湾台北大学附属医院影像学系
    5台湾台北大学附属医院内科

电子邮件：C. Hsu（[email protected]）

*通讯
台湾大学医学院肿瘤研究所徐氏博士台湾台北;台湾台北大学附属医院肿瘤科。
电子邮件：[email protected]

   
抽象
背景

来那度胺具有免疫调节和抗血管生成作用，在患者中具有中等的抗肿瘤功效。晚期肝细胞癌（HCC）
目标

探讨来那度胺疗效的潜在生物标志物作为HCC的二线治疗。
方法

合格的患者被诊断患有晚期HCC，记录在索拉非尼的进展和Child-Pugh A级肝功能。患者每4周在第1-21天口服25mg /天来那度胺。主要终点为6个月无进展生存率。早期甲胎蛋白反应被定义为在治疗前4周内甲胎蛋白水平从基线下降> 20％。使用动态造影增强磁共振成像评估的血管反应定义为治疗2周后Ktrans> 40％下降。还分析了外周血淋巴细胞亚群的百分比。
结果

55名患者入组。反应率为13％，疾病控制率为53％。 6个月无进展生存率为9.1％。中位无进展和总生存期分别为1.8个月和8.9个月。早期甲胎蛋白反应与疾病控制率（76％vs 22％，P = 0.001）和更长的无进展生存期（P = 0.020）显着相关。血管反应与任何治疗结果无关。具有高预处理B细胞百分比的患者更有可能进行疾病控制（70％对36％，P = 0.010），并且表现出更长的无进展生存期（P <0.001）和总生存期（P = 0.042） ）。
结论

来那度胺显示中度活动作为晚期HCC的二线治疗。应进一步探索其免疫调节作用（www.clinicaltrials.gov NCT01545804）。