Subgroup analysis of the ORR.

BackgroundThis study aimed to investigate the therapeutic efficacy and safety of Traditional medicine preparations (TMPs) given in combination with vascular endothelial growth factor receptor (VEGFR)-associated multi-targeted tyrosine kinase inhibitors (TKIs) for the treatment of middle to advanced-stage primary liver cancer (PLC).MethodsThis systematic literature survey employed 10 electronic databases and 2 clinical trial registration platforms to identify relevant studies on the use of TMPs + VEGFR-TKIs to treat patients with middle-advanced PLC. Furthermore, a meta-analysis was performed following the PRISMA guidelines using the risk ratio (RR) at 95% confidence intervals (CI) or standardized mean difference as effect measures.ResultsA total of 26 studies comprising 1678 middle-advanced PLC patients were selected. The meta-analysis revealed that compared with VEGFR-TKI mono-treatment, the co-therapy of TMPs + VEGFR-TKIs considerably enhanced the objective response rate (RR = 1.49, 95% CI: 1.31–1.69), disease control rate (RR = 1.23, 95% CI: 1.16–1.30), and one-year overall survival (RR = 1.49, 95% CI: 1.28–1.74). Furthermore, the co-therapy was associated with reduced incidences of liver dysfunction (RR = 0.64, 95% CI: 0.45–0.91), proteinuria (RR = 0.43, 95% CI: 0.24–0.75), hypertension (RR = 0.66, 95% CI: 0.53–0.83), hand-foot skin reactions (RR = 0.63, 95% CI: 0.49–0.80), myelosuppression (RR = 0.63, 95% CI: 0.46–0.87), and gastrointestinal reactions (RR = 0.64, 95% CI: 0.45–0.92). Moreover, the co-therapy indicated no increase in the incidences of rash and fatigue.ConclusionThis systematic analysis revealed that co-therapy with TMPs + VEGFR-TKIs has a higher effectiveness and safety profile for treating middle-advanced PLC patients. However, further validation using randomized control trials is required.PROSPERO registration noCRD42022350634.

背景 本研究旨在探讨传统中药制剂（Traditional medicine preparations, TMPs）联合血管内皮生长因子受体（vascular endothelial growth factor receptor, VEGFR）相关多靶点酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）治疗中晚期原发性肝癌（primary liver cancer, PLC）的疗效与安全性。方法 本系统文献调研共检索10个电子数据库与2个临床试验注册平台，以筛选关于TMPs联合VEGFR-TKIs治疗中晚期PLC患者的相关研究。随后遵循PRISMA指南开展荟萃分析，以风险比（risk ratio, RR）及95%置信区间（confidence interval, CI）或标准化均差作为效应量指标。结果 最终共纳入26项研究，涉及1678例中晚期PLC患者。荟萃分析结果显示，相较于单纯VEGFR-TKI治疗，TMPs联合VEGFR-TKIs的联合治疗可显著提升客观缓解率（RR=1.49, 95%CI: 1.31–1.69）、疾病控制率（RR=1.23, 95%CI: 1.16–1.30）及1年总生存期（RR=1.49, 95%CI: 1.28–1.74）。此外，联合治疗可降低肝功能异常（RR=0.64, 95%CI: 0.45–0.91）、蛋白尿（RR=0.43, 95%CI: 0.24–0.75）、高血压（RR=0.66, 95%CI: 0.53–0.83）、手足皮肤反应（RR=0.63, 95%CI: 0.49–0.80）、骨髓抑制（RR=0.63, 95%CI: 0.46–0.87）及胃肠道不良反应（RR=0.64, 95%CI: 0.45–0.92）的发生率，且未增加皮疹与疲劳的发生风险。结论 本系统分析表明，TMPs联合VEGFR-TKIs治疗中晚期PLC患者具有更优的疗效与安全性，但仍需开展随机对照试验进一步验证该结论。PROSPERO注册编号：CRD42022350634。