Supplementary Material for: Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma

<b><i>Background:</i></b> The present study aimed to assess the efficacy and safety of lenvatinib and verify the possibility of lenvatinib for the expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma (HCC) in real-world practice, primarily focusing on the population that was excluded in the REFLECT trial. <b><i>Methods:</i></b> We retrospectively collected data on patients with advanced HCC who were administered lenvatinib in 7 institutions in Japan. <b><i>Results:</i></b> Of 152 advanced HCC patients, 95 and 57 patients received lenvatinib in first-line and second- or later-line systemic therapies, respectively. The median progression-free survival in Child-Pugh class A patients was nearly equal between first- and second- or later-line therapies (5.2 months; 95% CI 3.7–6.9 for first line, 4.8 months; 95% CI 3.8–5.9 for second or later line, <i>p</i> = 0.933). According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate of 27 patients (18%) who showed a high burden of intrahepatic lesions (i.e., main portal vein and/or bile duct invasion or 50% or higher liver occupation) at baseline radiological assessment was 41% and similar with that of other population. The present study included 20 patients (13%) with Child-Pugh class B. These patients observed high frequency rates of liver function-related adverse events due to lenvatinib. The 8-week dose intensity of lenvatinib had a strong correlation with liver function according to both the Child-Pugh and albumin – bilirubin scores. <b><i>Conclusion:</i></b> Lenvatinib had potential benefits for patients with advanced HCC with second- or later-line therapies and a high burden of intrahepatic lesions. Dose modification should be paid increased attention among patients with poor liver function, such as Child-Pugh class B patients.

<b><i>背景:</i></b> 本研究旨在评估仑伐替尼（lenvatinib）的疗效与安全性，并验证基于REFLECT试验的仑伐替尼拓展适应证在真实世界中晚期肝细胞癌（hepatocellular carcinoma，HCC）患者中的应用可能性，重点聚焦REFLECT试验中排除的人群。<b><i>方法:</i></b> 本研究回顾性收集了日本7家医疗机构中接受仑伐替尼治疗的晚期肝细胞癌患者的临床数据。<b><i>结果:</i></b> 本研究共纳入152例晚期肝细胞癌患者，其中95例接受仑伐替尼一线全身治疗，57例接受二线及以上全身治疗。Child-Pugh A级患者中，一线治疗组与二线及以上治疗组的中位无进展生存期基本相当（一线组：5.2个月，95%置信区间3.7~6.9；二线及以上组：4.8个月，95%置信区间3.8~5.9，<i>p</i> = 0.933）。根据实体瘤疗效评价修订标准（modified Response Evaluation Criteria in Solid Tumors），基线影像学评估提示肝内病变负荷较高（即主门静脉和/或胆管受侵，或肝脏占位≥50%）的27例患者（占比18%）的客观缓解率为41%，与其他人群的客观缓解率相近。本研究纳入20例Child-Pugh B级患者（占比13%），该类患者因仑伐替尼引发肝功能相关不良事件的发生率较高。仑伐替尼的8周给药强度与Child-Pugh评分及白蛋白-胆红素评分均呈显著相关性。<b><i>结论:</i></b> 仑伐替尼用于晚期肝细胞癌的二线及以上治疗，以及肝内病变负荷较高的患者时，均展现出潜在获益。对于肝功能较差的患者（如Child-Pugh B级患者），应更加重视给药剂量调整。