Qin Jian, Huang Yusheng, Zhou Hanjing, Yi Shouhui
Department of Oncology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Oncology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Oncol. 2022 Apr 8;12:807102. doi: 10.3389/fonc.2022.807102. eCollection 2022.
The aim of the study is to compare the efficacy and safety of monotherapy with a sequential immune checkpoint inhibitor (ICI) programmed cell death protein-1 (PD-1) and its combination with multi-target drug sorafenib after transcatheter arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).
We conducted a retrospective evaluation of patients with advanced HCC who had received sequential PD-1 sorafenib (duplex group, n = 25) or monotherapy PD-1 alone (PD-1 group, n = 41) after TACE during April 2018-September 2021. Propensity score matching (PSM) was applied to correct the selection bias, and 22 pairs were created. The objective response rate (ORR), duration of the overall response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events were analyzed for both groups.
After PSM, the median PFS (7.63 vs. 2.9 months; p = 0.0335) was significantly longer for the duplex group than for the PD-1 group. The median OS (21.63 vs. 16.43 months; p = 0.103) was longer for the duplex group than for the PD-1 group, albeit without any statistical difference. The CR rate, ORR, DCR, and PFS rates at the first, third, and sixth months were higher for the duplex group than for the PD-1 group, wherein the PFS rate of the third and sixth months were statistically different. The OS rates at the sixth, 12th, and 18th months were better for the duplex group than for the PD-1 group, while the 18th-month OS rate (54.5% vs. 33.9%, p = 0.030) were statistically different between them. The most common adverse events after TACE included liver function injury, leukocytopenia, and thrombocytopenia, albeit without any statistical differences between the groups. Cox regression analysis showed that sorafenib combined immunotherapy after TACE and the achieving of CR or PR during the treatment were independent factors affecting PFS. Moreover, CNLC stage-IIIa, TACE frequency ≤2, and achievement of CR or PR were independent influencing factors of OS.
Sequential PD-1 combined with sorafenib therapy after TACE for advanced HCC treatment is safe and effective, especially for patients with good initial treatment response, to further improve the disease prognosis.
本研究旨在比较经动脉化疗栓塞术(TACE)后,序贯免疫检查点抑制剂程序性细胞死亡蛋白-1(PD-1)单药治疗与联合多靶点药物索拉非尼治疗晚期肝细胞癌(HCC)的疗效和安全性。
我们对2018年4月至2021年9月期间接受TACE治疗后序贯使用PD-1联合索拉非尼(联合组,n = 25)或单独使用PD-1单药治疗(PD-1组,n = 41)的晚期HCC患者进行了回顾性评估。采用倾向评分匹配(PSM)来纠正选择偏倚,共形成22对。分析两组的客观缓解率(ORR)、总缓解持续时间(DOR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS)及不良事件。
PSM后,联合组的中位PFS(7.63个月 vs. 2.9个月;p = 0.0335)显著长于PD-1组。联合组的中位OS(21.63个月 vs. 16.43个月;p = 0.103)长于PD-1组,尽管无统计学差异。联合组在第1、3和6个月时的完全缓解(CR)率、ORR、DCR和PFS率均高于PD-1组,其中第3和6个月时的PFS率有统计学差异。联合组在第6、12和18个月时的OS率优于PD-1组,且两组在第18个月时的OS率有统计学差异(54.5% vs. 33.9%,p = 0.030)。TACE术后最常见的不良事件包括肝功能损伤、白细胞减少和血小板减少,尽管两组间无统计学差异。Cox回归分析显示,TACE术后索拉非尼联合免疫治疗以及治疗期间达到CR或部分缓解(PR)是影响PFS的独立因素。此外,中国肝癌临床分期(CNLC)IIIa期、TACE次数≤2次以及达到CR或PR是影响OS的独立因素。
TACE术后序贯使用PD-1联合索拉非尼治疗晚期HCC安全有效,尤其对于初始治疗反应良好的患者,可进一步改善疾病预后。