Xu Lin, Che Xu
Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
Front Oncol. 2024 Dec 2;14:1478596. doi: 10.3389/fonc.2024.1478596. eCollection 2024.
This study aims to evaluate the safety efficacy of combining the PD-1 antibody Tirelizumab with Sorafenib in the treatment of advanced hepatocellular carcinoma. Additionally we are committed to investigating the relationship between circulating tumor cell (CTC) counts/PD-L1 expression the prognosis of patients with advanced hepatocellular carcinoma.
This study included 32 patients with unresectable primary liver cancer who received treatment with Tislelizumab in combination with Sorafenib. Tislelizumab was administered via intravenous injection at a dose of 200 mg every 3 weeks, while Sorafenib was given orally at a dose of 400 mg twice daily. Patients were evaluated every 3 cycles (9 weeks) to assess the safety and efficacy of the treatment regimen. Prior to enrollment, all patients underwent CTC counting and assessment of PD-L1 expression in circulating tumor cells. The primary endpoint was the objective response rate (ORR), evaluated by the investigator according to the RECIST v1.1 criteria. Secondary endpoints aimed to assess the relationship between circulating tumor cell (CTC) counts or programmed death ligand 1 (PD-L1) expression and the prognosis of patients with advanced hepatocellular carcinoma.
As of November 2022, a total of 32 patients have been enrolled in the study and received combination treatment. Among the 32 patients, 31 (96.8%) tested positive for circulating tumor cells (CTCs), with counts ranging from 1 to 45 and a median of 7 (3, 11). PD-L1-positive CTCs were detected in 25 patients (78.1%). All 32 patients were followed up for 2 to 14 months, with a median follow-up time of 6 months. Correlation analysis revealed that distant metastasis, vascular invasion, and the presence of more than 5 CTCs were significantly associated with PD-L1-positive CTCs. The one-year overall survival rates for patients with PD-L1-positive CTCs and those with PD-L1-negative CTCs were 78.5% vs 64.3% (P = 0.309). Additionally, the one-year overall survival rates for the group with rising CTC counts compared to the group with stable or declining counts were 34.3% vs 90% (P = 0.063).
The combination of Tislelizumab and Sorafenib demonstrates promising antitumor activity in the first-line treatment of hepatocellular carcinoma, with a relatively high objective response rate (ORR) and acceptable safety profile. Baseline CTC PD-L1 positivity can serve as a predictive marker for selecting hepatocellular carcinoma patients for PD-1/PD-L1 blockade therapy, and dynamic measurement of CTC changes can be used to monitor treatment efficacy.
本研究旨在评估PD-1抗体替雷利珠单抗与索拉非尼联合治疗晚期肝细胞癌的安全性和疗效。此外，我们致力于研究循环肿瘤细胞（CTC）计数/PD-L1表达与晚期肝细胞癌患者预后之间的关系。
本研究纳入32例不可切除的原发性肝癌患者，接受替雷利珠单抗联合索拉非尼治疗。替雷利珠单抗通过静脉注射给药，剂量为每3周200mg，而索拉非尼口服给药，剂量为每日两次，每次400mg。每3个周期（9周）对患者进行评估，以评估治疗方案的安全性和疗效。在入组前，所有患者均进行了CTC计数和循环肿瘤细胞中PD-L1表达的评估。主要终点是客观缓解率（ORR），由研究者根据RECIST v1.1标准进行评估。次要终点旨在评估循环肿瘤细胞（CTC）计数或程序性死亡配体1（PD-L1）表达与晚期肝细胞癌患者预后之间的关系。
截至2022年11月，共有32例患者入组并接受联合治疗。在这32例患者中，31例（96.8%）循环肿瘤细胞（CTC）检测呈阳性，计数范围为1至45，中位数为7（3，11）。25例患者（78.1%）检测到PD-L1阳性的CTC。所有32例患者均随访2至14个月，中位随访时间为6个月。相关性分析显示，远处转移、血管侵犯和CTC数量超过5个与PD-L1阳性的CTC显著相关。PD-L1阳性的CTC患者和PD-L1阴性的CTC患者的一年总生存率分别为78.5%和64.3%（P = 0.309）。此外，CTC计数上升组与稳定或下降组相比，一年总生存率分别为34.3%和90%（P = 0.063）。
替雷利珠单抗和索拉非尼联合在肝细胞癌一线治疗中显示出有前景的抗肿瘤活性，客观缓解率（ORR）相对较高且安全性可接受。基线CTC PD-L1阳性可作为选择肝细胞癌患者进行PD-1/PD-L1阻断治疗的预测标志物，动态测量CTC变化可用于监测治疗效果。
