Background & Aims

Patients with hepatocellular carcinoma (HCC) secondary to chronic liver disease often require invasive procedures but frequently have thrombocytopenia. Lusutrombopag is an agonist of the thrombopoietin receptor that activates platelet production.

Methods

We performed an integrated analysis of data from 2 phase 3 trials (L-PLUS 1, Japan, October 2013 to May 2014, and L-PLUS 2, global, June 2015 to April 2017) that compared the efficacy and safety of lusutrombopag with placebo in patients with chronic liver disease, with and without HCC. Our analysis included patients with Eastern Cooperative Oncology Group grades of 0 or 1, Child–Pugh classes A or B, and a platelet count less than 50 × 10⁹/L who were scheduled to undergo invasive procedures in 9 to 14 days. Patients received lusutrombopag (3 mg) or placebo daily for 7 days or fewer before an invasive procedure. Imaging studies assessed treatment-emergent adverse events, including asymptomatic portal vein thrombosis. The primary end point was no requirement for platelet transfusion before the invasive procedure and rescue therapies for bleeding 7 days or fewer after the invasive procedure.

Results

The per-protocol population included 270 patients (95 with HCC). A significantly higher proportion of patients with HCC who received lusutrombopag achieved the primary end point (68.0%) vs patients who received placebo (8.9%) (P < .0001); in patients without HCC, these proportions were 77.0% vs 21.6% (P < .0001). Lusutrombopag reduced the need for platelet transfusions, increased platelet counts for 3 weeks, and reduced the number of bleeding events in patients with and without HCC compared with placebo. Risk of thrombosis was similar to that of placebo.

Conclusions

Patients with and without HCC receiving lusutrombopag had a reduction in the number of platelet transfusions before invasive procedures compared with patients receiving placebo, with no increase in thrombosis or bleeding. L-PLUS 1: JapicCTI-132323; L-PLUS 2: ClinicalTrials.gov number no: NCT02389621.

中文翻译：

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Lusutrombopag 可安全有效地治疗患有和不患有肝细胞癌的患者的血小板减少症。

背景与目标

继发于慢性肝病的肝细胞癌 (HCC) 患者通常需要侵入性手术，但经常出现血小板减少症。Lusutrombopag 是血小板生成素受体的激动剂，可激活血小板生成。

方法

我们对来自 2 项 3 期试验（L-PLUS 1，日本，2013 年 10 月至 2014 年 5 月，以及 L-PLUS 2，全球，2015 年 6 月至 2017 年 4 月）的数据进行了综合分析，比较了 lusutrombopag 与安慰剂的疗效和安全性慢性肝病患者，无论有无 HCC。我们的分析包括东部肿瘤协作组 0 或 1 级、Child-Pugh A 或 B 级、血小板计数低于 50 × 10 ^9的患者/L 计划在 9 至 14 天内接受侵入性手术。患者在侵入性手术前每天接受 lusutrombopag (3 mg) 或安慰剂治疗 7 天或更短时间。影像学研究评估了治疗中出现的不良事件，包括无症状门静脉血栓形成。主要终点是在侵入性手术前不需要输注血小板，以及在侵入性手术后 7 天或更短时间内对出血进行抢救治疗。

结果

符合方案的人群包括 270 名患者（95 名患有 HCC）。与接受安慰剂的患者 (8.9%) 相比，接受 Lusutrombopag 的 HCC 患者达到主要终点 (68.0%) 的比例显着更高 ( P < .0001)；在没有 HCC 的患者中，这些比例分别为 77.0% 和 21.6% ( P < .0001)。与安慰剂相比，Lusutrombopag 减少了血小板输注的需要，增加了 3 周的血小板计数，并减少了有和无 HCC 患者的出血事件数量。血栓形成的风险与安慰剂相似。

结论

与接受安慰剂的患者相比，接受 lusutrombopag 的患有和未患 HCC 的患者在侵入性手术前输注血小板的次数减少，血栓形成或出血没有增加。L-PLUS 1：JapicCTI-132323；L-PLUS 2：ClinicalTrials.gov 编号：NCT02389621。