Experience With Early Sorafenib Treatment With mTOR Inhibitors in Hepatocellular Carcinoma Recurring After Liver Transplantation
Experience With Early Sorafenib Treatment With mTOR Inhibitors in Hepatocellular Carcinoma Recurring After Liver Transplantation
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DOI：
10.1097/tp.0000000000002955
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发表时间：
2020-03-01
期刊：
影响因子：
6.2
通讯作者：
Lampertico, Pietro
中科院分区：
文献类型：
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作者：
Invernizzi, Federica;Iavarone, Massimo;Lampertico, Pietro
背景：索拉非尼(Sorafenib，SOR)目前用于肝移植(LT)后复发的肝细胞癌(肝细胞癌)，因为肝细胞癌不适合手术或局部治疗。我们评估了肝癌复发后早期应用SOR的安全性和有效性。方法：纳入2个中心(2008年1月至2018年6月)接受SOR治疗的所有肝移植术后复发的肝癌患者。收集基线和治疗中的数据。结果：纳入50名早期接受SOR治疗的肝移植后肝细胞癌复发的患者(74%的哺乳动物靶基因雷帕霉素抑制剂[mTORi]，54%的肝细胞癌在基线治疗)。在7.3(0.3-88)个月的SOR期间，所有患者至少有一次不良事件(AE)，56%的患者分级为3-4级。SOR减少了68%，是AEs减少的主要原因，84%停止了(60%症状进展，33%AE)。目的缓解率为16%，稳定期为50%。放射学进展的中位时间为6个月(95%可信区间[CI]，4-8)。33名患者(69%)死亡，94%死于肝细胞癌进展。中位总生存期(OS)为18个月(95%CI，8~27)，5年OS为18%(95%CI，4%~32%)。预测OS的基线因素是SOR+mTORI(危险比，0.4；95%CI，0.2~0.9；P=0.04)、既往治疗(HR，0.3；95%CI，0.2~0.7；P=0.003)和甲胎蛋白和GT；100 ng/mL(HR，2.5；95%CI，1.1~5.0，P=0.02)。在多因素分析中，肝癌治疗是唯一的独立预测因素(HR，0.4；95%CI 0.2-1.0；P=0.04)。结论：早期和联合应用SOR和mTORI治疗具有良好的安全性，但其有效性应通过先前研究或更大规模研究的荟萃分析来证实。肝细胞癌的根治治疗是影响OS的唯一独立预测因素。
Background.Sorafenib (SOR) is currently used for hepatocellular carcinoma (HCC) recurring after liver transplantation (LT) when HCC is unsuitable for surgical/locoregional treatments. We evaluated safety and effectiveness of early introduction of SOR after HCC-recurrence.Methods.All patients with HCC-recurrence after LT treated with SOR in 2 centers were included (January 2008 to June 2018). Baseline and on-treatment data were collected.Results.Fifty patients early treated with SOR for HCC-recurrence after LT (74% mammalian target of rapamycin inhibitor [mTORi], 54% HCC-treated at baseline) were enrolled. During 7.3 (0.3-88) months of SOR, all patients had at least one adverse event (AE), 56% graded 3-4. SOR was reduced in 68%, being AEs the main cause of reduction, and discontinued in 84% (60% symptomatic progression, 33% AE). Objective response was obtained in 16% and stable disease in 50%. Median time to radiological progression was 6 months (95% confidence Interval [CI], 4-8). Thirty-three patients (69%) died, 94% for HCC progression. Median overall survival (OS) was 18 months (95% CI, 8-27); 5-year OS was 18% (95% CI, 4%-32%). Baseline predictors of OS were SOR+mTORi (hazard ratio [HR], 0.4; 95% CI, 0.2-0.9; P = 0.04), previous curative treatments (HR, 0.3; 95% CI, 0.2-0.7; P = 0.003) and alpha-fetoprotein > 100 ng/mL (HR, 2.5; 95% CI, 1.1-5.0, P = 0.02). At multivariate analysis, HCC curative treatment was the only independent predictor (HR, 0.4; 95% CI 0.2-1.0; P = 0.04).Conclusions.Early and combined treatment with SOR and mTORi resulted in a favorable safety profile, while its effectiveness should be confirmed by meta-analysis of previous studies or by larger studies. Curative treatment for HCC resulted the only independent predictor of OS.