A randomized, double-blind, placebo-controlled, phase 3 study of tivantinib in Japanese patients with MET-high hepatocellular carcinoma.
A randomized, double-blind, placebo-controlled, phase 3 study of tivantinib in Japanese patients with MET-high hepatocellular carcinoma.
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DOI：
10.1111/cas.14582
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发表时间：
2020-10
期刊：
影响因子：
5.7
通讯作者：
Furuse J
中科院分区：
文献类型：
--
作者：
Kudo M;Morimoto M;Moriguchi M;Izumi N;Takayama T;Yoshiji H;Hino K;Oikawa T;Chiba T;Motomura K;Kato J;Yasuchika K;Ido A;Sato T;Nakashima D;Ueshima K;Ikeda M;Okusaka T;Tamura K;Furuse J
既往一项肝细胞癌随机II期研究显示，c-Met抑制剂tivantinib作为二线治疗可显著延长肿瘤样本高表达c-Met（MET-high）亚群的无进展生存期。因此，进行了这项III期研究，以评价tivantinib作为MET-高肝细胞癌日本患者二线治疗的疗效。这项随机、双盲、安慰剂对照研究在日本的60家临床试验机构进行。既往接受过一次索拉非尼治疗的肝细胞癌患者和MET-高肿瘤样本的患者有资格入选。登记的患者以2：1的比例随机分配到tivantinib或安慰剂组，并接受每日两次口服tivantinib（120 mg bid）或安慰剂治疗，直至符合停药标准。主要终点是无进展生存期，而次要终点包括总生存期和安全性。在2014年1月至2016年6月期间，386名患者提供了知情同意书，195名患者被随机分配到tivantinib组（n = 134）或安慰剂组（n = 61）。tivantinib组和安慰剂组的中位无进展生存期分别为2.8（95%置信区间：2.7 - 2.9）个月和2.3（1.5 - 2.8）个月（风险比= 0.74，95%置信区间：0.52 - 1.04，P = 0.082）。tivantinib组和安慰剂组的中位总生存期分别为10.3（95%置信区间：8.1 - 11.6）和8.5（6.2 - 11.4）个月（风险比= 0.82，95%置信区间：0.58 - 1.15）。最常见的tivantinib相关≥3级不良事件为中性粒细胞减少（31.6%）、白细胞减少（24.8%）和贫血（12.0%）。本研究未证实tivantinib作为日本MET-高肝细胞癌患者的二线治疗的显著疗效。（NCT02029157）。JET-HCC的结果。
A previous randomized phase 2 study of hepatocellular carcinoma revealed that the c‐Met inhibitor tivantinib as second‐line treatment significantly prolonged progression‐free survival in a subpopulation whose tumor samples highly expressed c‐Met (MET‐high). Accordingly, this phase 3 study was conducted to evaluate the efficacy of tivantinib as a second‐line treatment for Japanese patients with MET‐high hepatocellular carcinoma. This randomized, double‐blind, placebo‐controlled study was conducted at 60 centers in Japan. Hepatocellular carcinoma patients with one prior sorafenib treatment and those with MET‐high tumor samples were eligible for inclusion. Registered patients were randomly assigned to either the tivantinib or placebo group at a 2:1 ratio and were treated with twice‐a‐day oral tivantinib (120 mg bid) or placebo until the discontinuation criteria were met. The primary endpoint was progression‐free survival while the secondary endpoints included overall survival and safety. Between January 2014 and June 2016, 386 patients provided consent, and 195 patients were randomized to the tivantinib (n = 134) or placebo (n = 61) group. Median progression‐free survival was 2.8 (95% confidence interval: 2.7‐2.9) and 2.3 (1.5‐2.8) mo in the tivantinib and placebo groups, respectively (hazard ratio = 0.74, 95% confidence interval: 0.52‐1.04, P = .082). Median overall survival was 10.3 (95% confidence interval: 8.1‐11.6) and 8.5 (6.2‐11.4) mo in the tivantinib and placebo group, respectively (hazard ratio = 0.82, 95% confidence interval: 0.58‐1.15). The most common tivantinib‐related grade ≥3 adverse events were neutropenia (31.6%), leukocytopenia (24.8%), and anemia (12.0%). This study did not confirm the significant efficacy of tivantinib as a second‐line treatment for Japanese patients with MET‐high hepatocellular carcinoma. (NCT02029157). Results of JET‐HCC.
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