Cancer Centre of Bayi Hospital, Nanjing Chinese Medicine University, Nanjing, China.
Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, China.
J Clin Oncol. 2021 Sep 20;39(27):3002-3011. doi: 10.1200/JCO.21.00163. Epub 2021 Jun 29.
Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC.
This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients.
Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 3.6 months ( .0570). The objective response rate was 4.6% 2.7% ( = .2448), and the disease control rate was 30.8% 28.7% (FAS; = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] 165 [50%]; .0018).
Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.
多纳非尼（一种新型多激酶抑制剂，索拉非尼的氘代衍生物）在 I 期和 Ib 期肝细胞癌（HCC）研究中显示出疗效。本研究比较了多纳非尼与索拉非尼作为晚期 HCC 一线治疗的疗效和安全性。
这项开放标签、随机、平行对照、多中心的 II/III 期试验纳入了来自中国 37 个中心的不可切除或转移性 HCC、Child-Pugh 评分≤7 且无既往系统治疗的患者。患者按 1:1 随机分配接受口服多纳非尼（0.2 g）或索拉非尼（0.4 g）每日两次，直到无法耐受毒性或疾病进展。主要终点为总生存期（OS），检测非劣效性和优效性。疗效主要在全分析集（FAS）中评估，安全性在所有接受治疗的患者中评估。
2016 年 3 月 21 日至 2018 年 4 月 16 日，668 例（意向治疗）患者被随机分配至多纳非尼和索拉非尼治疗组；FAS 分别纳入 328 例和 331 例患者。多纳非尼治疗的中位 OS 明显长于索拉非尼（FAS；12.1 个月 vs. 10.3 个月；风险比，0.831；95%CI，0.699 至 0.988；P=.0245）；意向治疗人群中，多纳非尼也显示出优于索拉非尼的 OS 结果。中位无进展生存期为 3.7 个月 vs. 3.6 个月（P=.0570）。客观缓解率为 4.6% vs. 2.7%（P=.2448），疾病控制率为 30.8% vs. 28.7%（FAS；P=.5532）。接受多纳非尼治疗的患者中，药物相关≥3 级不良事件发生率明显低于接受索拉非尼治疗的患者（125 例[38%] vs. 165 例[50%]；P=.0018）。
多纳非尼在改善 OS 方面优于索拉非尼，在晚期 HCC 中国患者中具有良好的安全性和耐受性，有望成为这些患者的一种潜在一线单药治疗选择。
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