Kudo Masatoshi, Ueshima Kazuomi, Chan Stephan, Minami Tomohiro, Chishina Hirokazu, Aoki Tomoko, Takita Masahiro, Hagiwara Satoru, Minami Yasunori, Ida Hiroshi, Takenaka Mamoru, Sakurai Toshiharu, Watanabe Tomohiro, Morita Masahiro, Ogawa Chikara, Wada Yoshiyuki, Ikeda Masafumi, Ishii Hiroshi, Izumi Namiki, Nishida Naoshi
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama 589-8511, Japan.
State Key Laboratory of Translation Oncology, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong 111-1111, China.
Cancers (Basel). 2019 Jul 31;11(8):1084. doi: 10.3390/cancers11081084.
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 ( = 0.254) and -2.66 to -2.09 in the cTACE group ( < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; < 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, < 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.
尽管经动脉化疗栓塞术（TACE）是中期肝细胞癌（HCC）的标准治疗方法，但这是一种异质性很大的疾病，其中包括一部分无法从TACE治疗中获益的患者。目前，针对这部分患者的治疗策略在临床实践中仍是一项未满足的需求。在此，我们开展了一项概念验证研究，对于肿瘤较大或为多结节且超过七项标准的中期HCC患者，作为初始治疗，乐伐替尼可能是比TACE更有利的治疗选择。这项概念验证研究纳入了2006年1月至2018年12月期间连续接受乐伐替尼或传统TACE（cTACE）初始治疗的642例HCC患者。在这些患者中，选取176例作为初始治疗接受乐伐替尼或cTACE且符合入选标准（不可切除、超过七项标准、既往未接受过TACE/全身治疗、无血管侵犯、无肝外转移且肝功能为Child-Pugh A级）的患者进行研究。采用倾向评分匹配法对患者人口统计学特征进行调整。倾向评分匹配后，比较了30例接受乐伐替尼前瞻性治疗的患者（14例在临床试验中、1例在早期准入项目中、15例在真实世界环境中）和60例接受cTACE初始治疗的患者的结局。乐伐替尼组30例患者从基线至治疗结束时白蛋白-胆红素（ALBI）评分的变化为-2.61至-2.61（P = 0.254），cTACE组为-2.66至-2.09（P<0.01）。乐伐替尼组的客观缓解率显著高于cTACE组（73.3%对33.3%；P<0.001），无进展生存期的中位数也显著长于cTACE组（16.0个月对3.0个月；P<0.001）。乐伐替尼组的总生存期显著长于cTACE组（37.9个月对21.3个月；风险比：0.48，P<0.01）。对于肝功能为Child-Pugh A级、肿瘤较大或为多结节且超过七项标准的中期HCC患者，这类患者通常无法从TACE治疗中获益，乐伐替尼比TACE能带来更有利的结局。
