Background: Lenvatinib, a multikinase inhibitor, is an FDA-approved treatment for advanced hepatocellular carcinoma (HCC) in the first-line setting. Recent trial data have established atezolizumab plus bevacizumab as well as tremelimumab plus durvalumab as preferred first-line treatment options for advanced HCC. The role of lenvatinib following progression on immunotherapy in patients with advanced HCC remains unclear. Methods: We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010 and 2021 at the Mayo Clinic in Minnesota, Arizona, and Florida who received immunotherapy followed by lenvatinib. Median overall survival and progression-free survival analyses were performed using the Kaplan–Meier method, and responses were determined using RECIST 1.1. Adverse events were determined using CTCAE v 4.0. Results: We identified 53 patients with advanced HCC who received lenvatinib following progression on immunotherapy. Forty five (85%) patients had a Child Pugh class A at diagnosis, while 30 (58%) patients were still Child Pugh A at time of lenvatinib initiation. Lenvatinib was administered as a second-line treatment in 85% of the patients. The median PFS was 3.7 months (95% CI: 3.2–6.6), and the median OS from the time of lenvatinib initiation was 12.8 months (95% CI: 6.7–19.5). In patients with Child Pugh class A, the median OS and PFS was 14 and 5.2 months, respectively. Race, gender, and Child Pugh class was associated with OS on multivariate analysis. Discussion: Our study, using real-world data, suggests that patients benefit from treatment with lenvatinib following progression on immunotherapy in advanced HCC. The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown, and these results need to be validated in a clinical trial.
背景：仑伐替尼是一种多激酶抑制剂，已获美国食品药品监督管理局批准用于晚期肝细胞癌的一线治疗。近期临床试验数据已确立阿特珠单抗联合贝伐珠单抗以及曲美木单抗联合度伐利尤单抗作为晚期肝细胞癌的优选一线治疗方案。然而，对于免疫治疗进展后的晚期肝细胞癌患者，仑伐替尼的治疗作用尚不明确。方法：我们对2010年至2021年间在梅奥诊所（明尼苏达州、亚利桑那州和佛罗里达州分院）诊断为晚期肝细胞癌并接受免疫治疗后序贯仑伐替尼治疗的患者进行了多中心回顾性分析。采用Kaplan-Meier法计算中位总生存期和无进展生存期，并依据RECIST 1.1标准评估治疗反应。不良事件根据CTCAE v4.0标准判定。结果：共纳入53例免疫治疗进展后接受仑伐替尼治疗的晚期肝细胞癌患者。诊断时45例（85%）患者为Child-Pugh A级，而开始仑伐替尼治疗时仍有30例（58%）患者维持Child-Pugh A级。85%的患者将仑伐替尼作为二线治疗。中位无进展生存期为3.7个月（95% CI：3.2-6.6），自仑伐替尼治疗开始的中位总生存期为12.8个月（95% CI：6.7-19.5）。在Child-Pugh A级患者中，中位总生存期和无进展生存期分别为14个月和5.2个月。多变量分析显示种族、性别和Child-Pugh分级与总生存期相关。讨论：本研究基于真实世界数据表明，晚期肝细胞癌患者在免疫治疗进展后接受仑伐替尼治疗仍能获益。对于免疫治疗进展后的晚期肝细胞癌患者，最佳治疗序贯方案仍不明确，这些结果尚需通过临床试验进一步验证。
肿瘤(癌症)患者之家