背景:我们进行了荟萃分析和试验序贯分析(TSA),以比较以下肝细胞癌(HCC)患者治疗策略之间的疗效和不良事件(AE):TACE加酪氨酸激酶抑制剂(TKIs)和免疫检查点抑制剂(ICIs)(TACETI)与TACE加TKIs(TACET)。
方法:我们系统地搜索了PubMed,WebofScience,Cochrane图书馆,和Embase用于比较TACE+T+I和TACE+T治疗BCLC中期或晚期HCC的研究。客观反应率(ORR),无进展生存期(PFS),总生存期(OS),和AE作为结果。我们使用基于异质性评估结果的固定或随机效应模型,并使用ReviewManager5.3和Stata16.0进行荟萃分析。然后我们执行了TSA。
结果:这项研究共纳入了5项研究,共检查了425名患者。我们的荟萃分析显示,与TACE+T相比,TACE+T+I显著提高了ORR(风险比[RR]=1.53,95%置信区间[CI]=1.27-1.85,p<0.01),延长了中位PFS(平均差[MD]=4.51个月,95%CI=2.16-6.87,p<0.01)和中位OS(MD=5.75个月,95%CI=4.03-7.48,p<0.01)。TSA测试了这些结果是真实的,而不需要更大的信息大小。在AE中,与接受TACE+T治疗的患者相比,接受TACE+T+I治疗的患者更易发生高血压(RR=1.58,95%CI=1.05~2.40,p<0.05).然而,TSA建议需要更多病例来确认这一差异.关于其他AE,两组间无显著差异.
结论:TACE+T+I对ORR有较好的疗效,PFS,和OS比TACE+T作为BCLCB期和C期HCC的治疗,不良事件没有明显增加。基于这些发现,精心设计,建议进行大型RCT。
BACKGROUND: We conducted a meta-analysis and
trial sequential analysis (TSA) to compare the therapeutic efficacy and adverse events (AEs) between the following treatment strategies for patients with hepatocellular carcinoma (HCC): TACE plus tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) (TACE + T + I) versus
TACE plus TKIs (
TACE + T).
METHODS: We systematically searched PubMed, the Web of Science, the Cochrane Library, and Embase for studies comparing TACE + T + I and TACE + T for the treatment of BCLC intermediate- or advanced-stage HCC. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and AEs were included as outcomes. We used a fixed- or random-effects model based on the results of a heterogeneity evaluation and performed a meta-analysis using Review Manager 5.3 and Stata 16.0. We then carried out the TSA.
RESULTS: Five studies examining a total of 425 patients were included in this
study. Our meta-analysis revealed that, compared to
TACE + T,
TACE + T + I significantly improved the ORR (risk ratio [RR] = 1.53, 95% confidence interval [CI] = 1.27-1.85, p < 0.01) and extended both the median PFS (mean difference [MD] = 4.51 months, 95% CI = 2.16-6.87, p < 0.01) and median OS (MD = 5.75 months, 95% CI = 4.03-7.48, p < 0.01). These results were tested to be true by the TSA without requiring a larger information size. Among AEs, hypertension tended to occur more often in patients treated with TACE + T + I than in those treated with TACE + T (RR = 1.58, 95% CI = 1.05-2.40, p < 0.05). However, the TSA suggested that additional cases are necessary to confirm this difference. Regarding the other AEs, no significant differences were detected between the two groups.
CONCLUSIONS: TACE + T + I showed better effects on the ORR, PFS, and OS than
TACE + T as a treatment for BCLC stages B and C HCC, without an obvious increase in the AEs. Based on these findings, well-designed, large RCTs are suggested.