Supplementary Material for: Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

<b><i>Introduction/Objective:</i></b> Lenvatinib demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Considering the discrepancies in patients between clinical trial data and daily practice, an account of practical experience is needed. <b><i>Methods:</i></b> We conducted a multicenter retrospective analysis in which 3 tertiary referral centers participated. A total of 92 patients with advanced HCC treated with lenvatinib between September 2018 and January 2020 were analyzed. <b><i>Results:</i></b> Lenvatinib was used as the first-line therapy for 67 (72.8%) patients, and for 25 (27.2%) patients previously treated with other systemic therapy including immune checkpoint inhibitors. At the time of initiation of lenvatinib, 74 (80.4%) and 18 (19.6%) patients were classified as Child-Pugh A and B, respectively. Thirty-five patients (38.0%) had extensive disease that would have excluded them from the REFLECT trial. In the Child-Pugh A group, the response rate graded according to the Response Evaluation Criteria in Solid Tumors v1.1 was 21.1%, median progression-free survival (PFS) was 4.6 (95% confidence interval [CI] 3.1–6.1) months, and overall survival (OS) was 10.7 (95% CI 4.8–16.5) months for patients treated with first-line lenvatinib (<i>n</i> = 57). With second- or later-line lenvatinib (<i>n</i> = 17), median PFS and OS were 4.1 (95% CI 3.1–5.1) and 6.4 (95% CI 5.1–7.7) months, respectively. In the Child-Pugh B group (<i>n</i> = 18), median PFS and OS were 2.6 (95% CI 0.6–4.6) and 5.3 (95% CI 2.0–8.5) months, respectively. The most common grade 3–4 toxicities were hyperbilirubinemia (<i>n</i> = 8; 8.7%), AST elevation (<i>n</i> = 6; 6.5%), and diarrhea (<i>n</i> = 5; 5.4%) across all study patients. <b><i>Conclusions:</i></b> In this real-world study, lenvatinib was found to be well tolerated and effective in more heterogeneous HCC patient populations.

**引言/研究目的**：仑伐替尼（Lenvatinib）在随机III期REFLECT试验中，于晚期肝细胞癌（hepatocellular carcinoma, HCC）患者中展现出良好的疗效与安全性。鉴于临床试验人群与日常临床实践患者间存在差异，亟需总结实际诊疗经验。**研究方法**：本研究开展多中心回顾性分析，共有3家三级转诊中心参与。本研究分析了2018年9月至2020年1月期间接受仑伐替尼治疗的92例晚期肝细胞癌患者。**研究结果**：67例（72.8%）患者将仑伐替尼作为一线治疗方案，另有25例（27.2%）患者此前已接受包括免疫检查点抑制剂（immune checkpoint inhibitors）在内的其他系统性治疗。在仑伐替尼治疗启动时，74例（80.4%）患者的Child-Pugh分级为A级，18例（19.6%）为B级。35例（38.0%）患者存在广泛病变，这类患者本应被排除在REFLECT试验之外。在接受一线仑伐替尼治疗的Child-Pugh A级患者亚组（n=57）中，按实体瘤疗效评价标准1.1版（Response Evaluation Criteria in Solid Tumors v1.1）评估的客观缓解率为21.1%，中位无进展生存期（progression-free survival, PFS）为4.6个月（95%置信区间[CI] 3.1~6.1），中位总生存期（overall survival, OS）为10.7个月（95%CI 4.8~16.5）。对于接受二线及以上仑伐替尼治疗的患者亚组（n=17），中位PFS和OS分别为4.1个月（95%CI 3.1~5.1）和6.4个月（95%CI 5.1~7.7）。在Child-Pugh B级患者亚组（n=18）中，中位PFS和OS分别为2.6个月（95%CI 0.6~4.6）和5.3个月（95%CI 2.0~8.5）。所有研究患者中最常见的3~4级不良事件为高胆红素血症（n=8；8.7%）、天门冬氨酸氨基转移酶（AST）升高（n=6；6.5%）以及腹泻（n=5；5.4%）。**研究结论**：本项真实世界研究显示，在异质性更强的肝细胞癌患者群体中，仑伐替尼耐受性良好且疗效确切。