Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child-Pugh A Liver Function: A Proof-Of-Concept Study
Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child-Pugh A Liver Function: A Proof-Of-Concept Study
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DOI：
10.3390/cancers11081084
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发表时间：
2019-08-01
期刊：
影响因子：
5.2
通讯作者：
Nishida, Naoshi
中科院分区：
文献类型：
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作者：
Kudo, Masatoshi;Ueshima, Kazuomi;Nishida, Naoshi
虽然经导管动脉化疗栓塞（TACE）是中期肝细胞癌（HCC）的标准治疗方法，但这是一种很大程度上异质性的疾病，包括一个不能从TACE中获益的亚组患者。这一亚组患者的治疗策略目前在临床实践中仍未得到满足。在这里，我们进行了一项概念验证研究，表明lenvatinib可能是一个比TACE更有利的治疗选择，作为超过7个标准的大或多结节肿瘤的中期HCC患者的初始治疗。这项概念验证研究包括2006年1月至2018年12月期间连续642例HCC患者，最初接受lenvatinib或传统TACE （cTACE）治疗。在这些患者中，176名接受lenvatinib或cTACE作为初始治疗并符合资格标准（不可切除，超过7级标准，既往无TACE/全身治疗，无血管侵犯，无肝外扩散和Child-Pugh A肝功能）的患者被选中参加研究。倾向评分匹配用于调整患者人口统计学。在倾向评分匹配后，比较了30例预期使用lenvatinib治疗的患者（14例临床试验，1例早期进入项目，15例现实环境）和60例初始使用cTACE治疗的患者的结果。lenvatinib组30例患者ALBI评分从基线到治疗结束的变化为-2.61 ~ -2.61 (p = 0.254)， cTACE组30例患者ALBI评分从基线到治疗结束的变化为-2.66 ~ -2.09 （p < 0.01）。lenvatinib组的客观缓解率明显高于cace组（73.3% vs. 33.3%, p < 0.001），中位无进展生存期明显高于cace组（16.0 vs. 3.0个月，p < 0.001）。lenvatinib组的总生存期明显长于cTACE组（37.9个月vs. 21.3个月；风险比：0.48,p < 0.01）。对于大或多结节的中期HCC患者，其肝功能超过Child-Pugh A - 7标准，通常不能从TACE中获益，lenvatinib提供比TACE更有利的结果。
Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria (unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function) were selected for the study. Propensity score matching was used to adjust for patient demographics. After propensity-score matching, the outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, one in an early access program and 15 in real world settings) and 60 patients treated with cTACE as the initial treatment was compared. The change of albumin-bilirubin (ALBI) score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in the lenvatinib group (p = 0.254) and -2.66 to -2.09 in the cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides a more favorable outcome than TACE.