Wang Lei, Lin Li, Zhou Wei
Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.
Pharmacol Ther. 2024 May;257:108634. doi: 10.1016/j.pharmthera.2024.108634. Epub 2024 Mar 16.
The study aims to evaluate the benefits and potential adverse effects of transarterial chemoembolization (TACE) combined with lenvatinib and programmed cell death 1 (PD-1) protein inhibitors in the treatment of advanced hepatocellular carcinoma (HCC). A systematic literature search of several databases for relevant studies, published from inception up to May 2023, was performed. Clinical trials investigating TACE combined with lenvatinib and PD-1 inhibitors compared with other treatment regimens for advanced HCC were included. Data were pooled using fixed- or random-effects models and expressed as hazard ratios (HRs) or risk ratios (RRs) with corresponding 95% confidence interval (CI). Trial sequential analysis was used to determine whether the study results were sufficiently conclusive. Totally thirteen cohort studies comprising 1279 patients were included. The combined use of TACE, lenvatinib, and PD-1 inhibitors significantly improved overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) compared with other treatment regimens. The incidences of all-grade or grade ≥ 3 adverse events were comparable and did not differ significantly between the two groups. Prognostic factor analysis identified treatment options, portal vein tumor thrombus, extrahepatic metastasis, and Barcelona Clinic Liver Cancer (BCLC) stage as independent prognostic factors for OS. Extrahepatic metastasis, Child-Pugh score, and hepatic vein invasion emerged as independent prognostic factors for PFS. TSA suggested that the available data were adequate for drawing numerical conclusions regarding ORR and DCR. An approach combining TACE, lenvatinib, and PD-1 inhibitors appeared to offer significant improvements in OS, PFS, ORR, and DCR in patients with advanced HCC without significantly increasing the risk for all-grade adverse events.
本研究旨在评估经动脉化疗栓塞术（TACE）联合乐伐替尼及程序性细胞死亡蛋白1（PD-1）抑制剂治疗晚期肝细胞癌（HCC）的疗效及潜在不良反应。我们对多个数据库进行了系统的文献检索，纳入了从数据库建立至2023年5月发表的相关研究。纳入了比较TACE联合乐伐替尼及PD-1抑制剂与其他晚期HCC治疗方案的临床试验。采用固定效应模型或随机效应模型汇总数据，并以风险比（HR）或比值比（RR）及相应的95%置信区间（CI）表示。采用试验序贯分析来确定研究结果是否具有足够的说服力。共纳入13项队列研究，涉及1279例患者。与其他治疗方案相比，TACE、乐伐替尼及PD-1抑制剂联合使用显著改善了总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和疾病控制率（DCR）。两组间所有级别的或≥3级不良事件的发生率相当，无显著差异。预后因素分析确定治疗方案、门静脉癌栓、肝外转移和巴塞罗那临床肝癌（BCLC）分期为OS的独立预后因素。肝外转移、Child-Pugh评分和肝静脉侵犯是PFS的独立预后因素。试验序贯分析表明，现有数据足以得出关于ORR和DCR的数值结论。TACE、乐伐替尼及PD-1抑制剂联合使用似乎能显著改善晚期HCC患者的OS、PFS、ORR和DCR，且不会显著增加所有级别不良事件的风险。
