Department of Oncology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, China.
Eur Rev Med Pharmacol Sci. 2023 Feb;27(4):1494-1502. doi: 10.26355/eurrev_202302_31390.
The triplet regimen based on the programmed cell death 1 (PD1)/ programmed cell death ligand 1 (PDL1) inhibitors combined radiotherapy and antiangiogenic drugs is a novel therapeutic strategy for hepatocellular carcinoma. We conducted a meta-analysis to evaluate the efficacy and safety of the triplet therapeutic regimen in the treatment of hepatocellular carcinoma.
We searched scientific literature databases and clinical trial databases through October 31, 2022, for required studies. The pooled hazard ratio (HR) was used to analyze the overall survival (OS), progression-free survival (PFS), and the pooled relative risk (RR) was used to analyze the objective response rate (ORR), disease control rate (DCR), mortality rate (MR), and adverse events (AEs) through random or fixed effects model, 95% confidence interval (CI) was determined for all outcomes. Qualities of the included literature were assessed by MINORS Critical appraisal checklist. Funnel plot was used to assess publication bias in the included studies.
Five studies (3 single-arm and 2 non-randomized comparative trials), including 358 cases, were enrolled. Meta-analysis showed that the pooled ORR, DCR, and MR were 51% (95% CI: 34%-68%), 86% (95% CI: 69-102%), and 38% (95% CI: 18-59%), respectively. Compared with triplet regimen, the single or dual-combination treatments had shorter OS (HR=0.53, 95%: 0.34-0.83 via univariate analysis; HR=0.49, 95%: 0.31-0.78 via multivariable analysis) and PFS (HR=0.52, 95%: 0.35-0.77 via univariate analysis; HR=0.54, 95%: 0.36-0.80 via multivariable analysis). Common AEs to triplet regimens included skin reaction (17%), nausea/vomiting (27%), fatigue (23%), while severe AEs (10%), fever (18%), diarrhea (15%), and hypertension (5%) without statistically significant differences.
In the treatment of hepatocellular carcinoma, PD1/PDL1 inhibitors combined radiotherapy and antiangiogenic drugs achieved better survival benefits than alone or dual-combination regimens. In addition, the triple-combination therapy has tolerable safety.
基于程序性细胞死亡 1（PD-1）/程序性细胞死亡配体 1（PD-L1）抑制剂的三联方案联合放疗和抗血管生成药物是治疗肝细胞癌的一种新的治疗策略。我们进行了一项荟萃分析，以评估三联治疗方案在治疗肝细胞癌中的疗效和安全性。
我们通过科学文献数据库和临床试验数据库检索了截至 2022 年 10 月 31 日的所需研究。使用合并风险比（HR）分析总生存期（OS）、无进展生存期（PFS），使用合并相对风险（RR）分析客观缓解率（ORR）、疾病控制率（DCR）、死亡率（MR）和不良事件（AE），通过随机或固定效应模型进行分析，所有结果的 95%置信区间（CI）。通过 MINORS 关键评估清单评估纳入文献的质量。使用漏斗图评估纳入研究的发表偏倚。
共纳入 5 项研究（3 项单臂研究和 2 项非随机对照试验），共 358 例患者。荟萃分析显示，ORR、DCR 和 MR 分别为 51%（95%CI：34%-68%）、86%（95%CI：69%-102%）和 38%（95%CI：18%-59%）。与三联方案相比，单一或双重联合治疗的 OS 更短（HR=0.53，95%：单变量分析为 0.34-0.83；多变量分析为 0.49，95%：0.31-0.78）和 PFS（HR=0.52，95%：单变量分析为 0.35-0.77；多变量分析为 0.54，95%：0.36-0.80）。三联方案常见的不良反应包括皮肤反应（17%）、恶心/呕吐（27%）、疲劳（23%），严重不良反应（10%）、发热（18%）、腹泻（15%）和高血压（5%），但无统计学差异。
在治疗肝细胞癌方面，PD-1/PD-L1 抑制剂联合放疗和抗血管生成药物比单独或双重联合治疗方案具有更好的生存获益。此外，三联疗法具有可耐受的安全性。
