Supplementary Material for: Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A retrospective multicenter study

Background Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria. Methods A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed. Results Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC. Conclusion Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

背景 仑伐替尼（Lenvatinib）已被批准用于晚期肝细胞癌（hepatocellular carcinoma, HCC）患者的一线治疗。目前，仑伐替尼在高加索人群真实世界患者中的疗效尚未得到充分明确。本研究旨在评估来自德国与奥地利的多中心队列（ELEVATOR）中仑伐替尼的治疗疗效。
方法 本研究对14家不同医疗中心接受一线系统性仑伐替尼治疗的205例患者开展了回顾性数据分析，对总生存期（Overall Survival, OS）、无进展生存期（Progression-Free Survival, PFS）、客观缓解率（Overall Response Rate, ORR）及不良事件发生率进行了评估与分析。
结果 真实世界场景下接受仑伐替尼治疗的患者，其中位总生存期达12.8个月，该结果与REFLECT研究的报道数据相当。符合REFLECT研究纳入标准的患者，其中位总生存期（mOS）与无进展生存期（mPFS）均优于未符合纳入标准的患者（mOS：15.6个月 vs 10.2个月，风险比（HR）0.55，95%置信区间（CI）0.38~0.81，P=0.002；mPFS：8.1个月 vs 4.8个月，HR 0.65，95%CI 0.46~0.91，P=0.0015）。相较于肝功能良好（ALBI分级1级）且体能状态佳（ECOG体能状态评分0分）的患者，白蛋白-胆红素（ALBI）分级提示肝功能受损，或ECOG体能状态评分≥2的患者，其生存期显著更短（HR 1.69，95%CI 1.07~2.66，P=0.023；HR 2.25，95%CI 1.19~4.23，P=0.012）。此外，本队列研究证实，大血管侵犯（HR 1.55，95%CI 1.02~2.37，P=0.041）与甲胎蛋白（AFP）≥200 ng/mL（HR 1.56，95%CI 1.03~2.34，P=0.034）均为晚期肝细胞癌患者的独立不良预后因素。
结论 总体而言，本研究数据证实了仑伐替尼作为晚期肝细胞癌一线治疗的疗效，且在该大型高加索人群真实世界回顾性队列中未发现新的或意外的不良事件，支持仑伐替尼可作为无法接受免疫治疗联合方案的晚期肝细胞癌一线患者的有效替代治疗选择。