Background/Aim: An effective postprogression treatment of lenvatinib (LEN) against unresectable hepatocellular carcinoma (u-HCC) has not been established. We aimed to elucidate the clinical role of continuing LEN beyond progression of disease (PD). Methods: From March 2018 to October 2020, 99 u-HCC patients, in whom PD was confirmed (male:female = 78:21, median age 72 years, Child-Pugh A = 99, Barcelona Clinic Liver Cancer stage A:B:C = 2:43:54, LEN as first-line = 55), were enrolled (stopped LEN at PD [A group], n = 26; continued LEN beyond PD [B group], n = 73). Radiological response was evaluated with RECIST 1.1. Clinical features and prognostic factors for overall survival (OS) were retrospectively investigated using inverse probability weighting (IPW) calculated by propensity score. Results: Median time to progression, best response, and modified albumin-bilirubin grade (mALBI) at both baseline and PD did not show significant difference between the groups. Postprogression treatment in the A group was best supportive care in 17, sorafenib in 4, regorafenib in 3, ramucirumab in 1, and hepatic arterial infusion chemotherapy in 1. After adjusting with IPW, the B group showed better prognosis in regard to OS after PD and OS after introducing LEN than the A group (10.8/19.6 vs. 5.8/11.2 months, p #x3c; 0.001, respectively). In IPW-adjusted Cox hazard multivariate analysis, significant prognostic factors for OS after PD were mALBI 2b/3 at PD (HR 1.983, p = 0.021), decline of Eastern Cooperative Oncology Group performance status (ECOG PS) from baseline at PD (HR 3.180, p #x3c; 0.001), elevated alpha-fetoprotein (≥100 ng/mL) at introducing LEN (HR 2.511, p = 0.004), appearance of new extrahepatic metastasis (HR 2.396, p = 0.006), positive for hand-foot skin reaction (HFSR) before PD (any grade) (HR 0.292, p #x3c; 0.001), and continuing LEN beyond PD (HR 0.297, p #x3c; 0.001). Conclusion: When ECOG PS and hepatic reserve function permit, continuing LEN treatment beyond PD, especially in u-HCC patients showed HFSR during LEN treatment, might be a good therapeutic option, at least until a more effective drug as a postprogression treatment after LEN failure is developed.
Liver Cancer

中文翻译：

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Lenvatinib失败后如何解决肝细胞癌患者未满足的临床需求？

背景/目的：尚未确定有效的伦伐替尼（LEN）治疗不可切除的肝细胞癌（u-HCC）的有效后治疗方法。我们旨在阐明在疾病进展（PD）之后持续进行LEN的临床作用。方法： 2018年3月至2020年10月，确诊PD的99例u-HCC患者（男：女= 78:21，中位年龄72岁，Child-Pugh A = 99，巴塞罗那临床肝癌A：B期： C = 2：43：54，LEN为第一行= 55）（在PD处停止LEN [A组]， n = 26；在PD​​以后超出LEN [B组]， n= 73）。放射反应用RECIST 1.1进行评估。使用倾向评分计算的逆概率加权（IPW）回顾性研究总体生存（OS）的临床特征和预后因素。结果：基线和PD的中位进展时间，最佳反应和改良的白蛋白-胆红素等级（mALBI）在两组之间无显着差异。A组进行进展后治疗的最佳支持治疗为17例，索拉非尼4例，瑞戈非尼3例，雷莫拉单抗1例，肝动脉灌注化疗1例。IPW调整后，B组在PD后OS方面显示出更好的预后和A组相比，引入LEN后的OS和OS（10.8 / 19.6 vs. 5.8 / 11.2个月，p＃x3c; 分别为0.001）。在IPW调整的Cox危害多因素分析中，PD后OS的重要预后因素为PD时mALBI 2b / 3（HR 1.983，p = 0.021），东部合作肿瘤小组的绩效状态（ECOG PS）相对于PD基线下降（HR 3.180 ，p＃x3c; 0.001），引入LEN时甲胎蛋白（≥100 ng / mL）升高（HR 2.511，p = 0.004），出现新的肝外转移（HR 2.396，p = 0.006），手部阳性PD（任何等级）之前的足部皮肤反应（HFSR）（HR 0.292，p＃x3c; 0.001），以及持续超过LEN超过PD（HR 0.297，p＃x3c; 0.001）。结论：当ECOG PS和肝储备功能允许时，在PD之后继续进行LEN治疗，尤其是在u-HCC患者中，在LEN治疗期间表现出HFSR，可能是一个很好的治疗选择，至少直到开发出一种更有效的药物作为LEN衰竭后的进展后治疗。
肝癌