Department of Radiation Oncology, Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Clinical Trials Unit, Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
JAMA Surg. 2024 Jun 1;159(6):616-624. doi: 10.1001/jamasurg.2024.0506.
Certain patients with hepatocellular carcinoma with portal vein tumor thrombus could benefit from surgical resection, and postoperative adjuvant therapy may lower the incidence of tumor recurrence.
To compare the efficacy and safety of sorafenib plus transarterial chemoembolization vs sorafenib alone as postoperative adjuvant therapy for patients with hepatocellular carcinoma with portal vein tumor thrombus.
DESIGN, SETTING, AND PARTICIPANTS: This was a phase 3, multicenter, randomized clinical trial conducted in 5 hospitals in China. A total of 158 patients were enrolled and randomized from October 2019 to March 2022, with a median follow-up of 28.4 months. Portal vein tumor thrombus was graded by the Cheng classification. Eligible patients with hepatocellular carcinoma with Cheng grade I to III portal vein tumor thrombus (ie, involving segmental or sectoral branches, right- or left-side branch, or main trunk of portal vein) were included.
Patients were randomly assigned 1:1 to receive transarterial chemoembolization with sorafenib or sorafenib alone as postoperative adjuvant therapy. Sorafenib treatment was started within 3 days after randomization, with an initial dose of 400 mg orally twice a day. In the transarterial chemoembolization with sorafenib group, transarterial chemoembolization was performed 1 day after the first administration of sorafenib.
The primary end point was recurrence-free survival. Efficacy was assessed in the intention-to-treat population and safety was assessed in patients who received at least 1 dose of study treatment.
Of 158 patients included, the median (IQR) age was 54 (43-61) years, and 140 (88.6%) patients were male. The median (IQR) recurrence-free survival was significantly longer in the transarterial chemoembolization with sorafenib group (16.8 [12.0-NA] vs 12.6 [7.8-18.1] months; hazard ratio [HR], 0.57; 95% CI, 0.39-0.83; P = .002). The median (IQR) overall survival was also significantly longer with transarterial chemoembolization with sorafenib than with sorafenib alone (30.4 [20.6-NA] vs 22.5 [15.4-NA] months; HR, 0.57; 95% CI, 0.36-0.91; P = .02). The most common grade 3/4 adverse event was hand-foot syndrome (23 of 79 patients in the transarterial chemoembolization with sorafenib group [29.1%] vs 24 of 79 patients in the sorafenib alone group [30.4%]). There were no treatment-related deaths in either group. The transarterial chemoembolization with sorafenib group did not show additional toxicity compared with the sorafenib monotherapy group.
In this study, the combination of sorafenib and transarterial chemoembolization as postoperative adjuvant therapy in patients with hepatocellular carcinoma with portal vein tumor thrombus resulted in longer recurrence-free survival and overall survival than sorafenib alone and was well tolerated.
ClinicalTrials.gov Identifier: NCT04143191.
某些伴有门静脉癌栓的肝细胞癌患者可能受益于手术切除，术后辅助治疗可能降低肿瘤复发的发生率。
比较索拉非尼联合经动脉化疗栓塞与索拉非尼单药治疗伴有门静脉癌栓的肝细胞癌患者作为术后辅助治疗的疗效和安全性。
设计、地点和参与者：这是一项在中国 5 家医院进行的 3 期、多中心、随机临床试验。共纳入 158 例患者，于 2019 年 10 月至 2022 年 3 月进行随机分组，中位随访 28.4 个月。门静脉癌栓采用 Cheng 分级。纳入的肝细胞癌患者伴有 Cheng 分级 I 至 III 级门静脉癌栓（即累及节段或扇段分支、右或左支或门静脉主干）。
患者被随机分配 1:1 接受索拉非尼联合经动脉化疗栓塞或索拉非尼单药作为术后辅助治疗。索拉非尼治疗在随机分组后 3 天内开始，初始剂量为 400 mg 口服，每日 2 次。在索拉非尼联合经动脉化疗栓塞组中，在首次服用索拉非尼后 1 天进行经动脉化疗栓塞。
主要终点是无复发生存率。在意向治疗人群中评估疗效，在至少接受 1 次研究治疗的患者中评估安全性。
在纳入的 158 例患者中，中位（IQR）年龄为 54（43-61）岁，140 例（88.6%）患者为男性。索拉非尼联合经动脉化疗栓塞组的中位（IQR）无复发生存期显著延长（16.8 [12.0-NA] vs 12.6 [7.8-18.1]个月；风险比[HR]，0.57；95%CI，0.39-0.83；P = .002）。索拉非尼联合经动脉化疗栓塞组的中位（IQR）总生存期也明显长于索拉非尼单药组（30.4 [20.6-NA] vs 22.5 [15.4-NA]个月；HR，0.57；95%CI，0.36-0.91；P = .02）。最常见的 3/4 级不良事件是手足综合征（索拉非尼联合经动脉化疗栓塞组 79 例患者中有 23 例[29.1%]，索拉非尼单药组 79 例患者中有 24 例[30.4%]）。两组均无治疗相关死亡。与索拉非尼单药组相比，索拉非尼联合经动脉化疗栓塞组并未显示出额外的毒性。
在这项研究中，索拉非尼联合经动脉化疗栓塞作为伴有门静脉癌栓的肝细胞癌患者的术后辅助治疗，与索拉非尼单药治疗相比，无复发生存期和总生存期更长，且耐受性良好。
ClinicalTrials.gov 标识符：NCT04143191。
