Survival in Patients With Recurrent Intermediate-Stage Hepatocellular Carcinoma: Sorafenib Plus TACE vs TACE Alone Randomized Clinical Trial.

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology Pub Date : 2024-08-01 DOI:10.1001/jamaoncol.2024.1831

Wenzhe Fan, Bowen Zhu, Shuling Chen, Yanqin Wu, Xiao Zhao, Liangliang Qiao, Zhen Huang, Rong Tang, Jinghua Chen, Wan Yee Lau, Minshan Chen, Jiaping Li, Ming Kuang, Zhenwei Peng

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引用次数: 0

Abstract

Importance: Transarterial chemoembolization (TACE) is commonly used to treat patients with recurrent intermediate-stage hepatocellular carcinoma (HCC) and positive microvascular invasion (MVI); however, TACE alone has demonstrated unsatisfactory survival benefits. A previous retrospective study suggested that TACE plus sorafenib (SOR-TACE) may be a better therapeutic option compared with TACE alone.

Objective: To investigate the clinical outcomes of SOR-TACE vs TACE alone for patients with recurrent intermediate-stage HCC after R0 hepatectomy with positive MVI.

Design, setting, and participants: In this phase 3, open-label, multicenter randomized clinical trial, patients with recurrent intermediate-stage HCC and positive MVI were randomly assigned in a 1:1 ratio via a computerized minimization technique to either SOR-TACE treatment or TACE alone. This trial was conducted at 5 hospitals in China, and enrolled patients from October 2019 to December 2021, with a follow-up period of 24 months. Data were analyzed from June 2023 to September 2023.

Interventions: Randomization to on-demand TACE (conventional TACE: doxorubicin, 50 mg, mixed with lipiodol and gelatin sponge particles [diameter: 150-350 μm]; drug-eluting bead TACE: doxorubicin, 75 mg, mixed with drug-eluting particles [diameter: 100-300 μm or 300-500 μm]) (TACE group) or sorafenib, 400 mg, twice daily plus on-demand TACE (SOR-TACE group) (conventional TACE: doxorubicin, 50 mg, mixed with lipiodol and gelatin sponge particles [diameter, 150-350 μm]; drug-eluting bead TACE: doxorubicin, 75 mg, mixed with drug-eluting particles [diameter: 100-300 μm or 300-500 μm]).

Main outcomes and measures: The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment.

Results: A total of 162 patients (median [range] age, 55 [28-75] years; 151 males [93.2%]), were randomly assigned to be treated with either SOR-TACE (n = 81) or TACE alone (n = 81). The median overall survival was significantly longer in the SOR-TACE group than in the TACE group (22.2 months vs 15.1 months; hazard ratio [HR], 0.55; P < .001). SOR-TACE also prolonged progression-free survival (16.2 months vs 11.8 months; HR, 0.54; P < .001), and improved the objective response rate when compared with TACE alone based on the modified Response Evaluation Criteria in Solid Tumors criteria (80.2% vs 58.0%; P = .002). Any grade adverse events were more common in the SOR-TACE group, but all adverse events responded well to treatment. No unexpected adverse events or treatment-related deaths occurred in this study.

Conclusions and relevance: The results of this randomized clinical trial demonstrated that SOR-TACE achieved better clinical outcomes than TACE alone. These findings suggest that combined treatment should be used for patients with recurrent intermediate-stage HCC after R0 hepatectomy with positive MVI.

Trial registration: ClinicalTrials.gov Identifier: NCT04103398.

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复发性中晚期肝细胞癌患者的生存率：索拉非尼加 TACE 与单用 TACE 随机临床试验。

重要性：经动脉化疗栓塞术（TACE）通常用于治疗复发性中晚期肝细胞癌（HCC）和微血管侵犯阳性（MVI）患者；然而，单用 TACE 的生存获益并不令人满意。先前的一项回顾性研究表明，与单用TACE相比，TACE加索拉非尼（SOR-TACE）可能是更好的治疗选择：目的：研究SOR-TACE与单用TACE治疗R0肝切除术后复发且MVI阳性的中晚期HCC患者的临床疗效：在这项三期、开放标签、多中心随机临床试验中，通过计算机最小化技术以 1:1 的比例将复发性中晚期 HCC 和 MVI 阳性患者随机分配到 SOR-TACE 治疗或单纯 TACE 治疗。该试验在中国 5 家医院进行，入组时间为 2019 年 10 月至 2021 年 12 月，随访期为 24 个月。数据分析时间为2023年6月至2023年9月：随机接受按需 TACE（传统 TACE：多柔比星 50 毫克，与脂肪碘和明胶海绵颗粒[直径：150-350 μm]混合；药物洗脱珠 TACE：多柔比星 75 毫克，与药物洗脱颗粒[直径：100-300 μm]混合）：100-300 μm 或 300-500 μm]）（TACE 组）或索拉非尼，400 毫克，每日两次，加按需 TACE（SOR-TACE 组）（传统 TACE：多柔比星，50 毫克，与脂碘和明胶海绵颗粒[直径：150-350 μm]混合；药物洗脱珠 TACE：多柔比星，75 毫克，与药物洗脱颗粒[直径：100-300 μm 或 300-500 μm]混合）。主要结果和测量指标：主要终点是总生存期，采用意向治疗分析法。对至少接受过一次治疗的患者进行安全性评估：共有162名患者（中位数[范围]年龄为55[28-75]岁；151名男性[93.2%]）被随机分配接受SOR-TACE（81人）或单独TACE（81人）治疗。SOR-TACE 组的中位总生存期明显长于 TACE 组（22.2 个月 vs 15.1 个月；危险比 [HR]，0.55；P 结论和意义：这项随机临床试验的结果表明，SOR-TACE 的临床疗效优于单用 TACE。这些研究结果表明，对于R0肝切除术后复发且MVI阳性的中晚期HCC患者，应采用联合治疗：试验注册：ClinicalTrials.gov Identifier：试验注册：ClinicalTrials.gov Identifier：NCT04103398。

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来源期刊

Jama Oncology Medicine-Oncology

CiteScore

37.50

自引率

1.80%

发文量

423

期刊介绍： At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science. Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers. We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.