PDF(Pubmed)
Abstract：
UNASSIGNED: This article is based on our previous research, which was presented at the 2023 ASCO Annual Meeting I and published in Journal of Clinical Oncology as Conference Abstract (JCO. 2023;41:e16148. doi: 10.1200/JCO.2023.41.16_suppl.e16148). Both anti-programmed death 1/ligand-1 (PD-1/L1) antibody + anti-vascular endothelial growth factor (VEGF) antibody (A + A) and anti-PD-1/L1 antibody + VEGF receptor (VEGFR)-targeted tyrosine kinase inhibitor (A + T) are effective first-line therapies for unresectable hepatocellular carcinoma. However, there lacks evidence from head-to-head comparisons between these two treatments. We conducted a network meta-analysis on the efficacy and safety of them.
UNASSIGNED: After a rigorous literature research, 6 phase III trials were identified for the final analysis, including IMbrave150, ORIENT-32, COSMIC-312, CARES-310, LEAP-002, and REFLECT. The experiments were classified into three groups: A + A, A + T, and intermediate reference group. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and incidence of treatment-related adverse events (TRAEs). Hazard ratio (HR) with 95% confidence intervals (CI) for OS and PFS, odds ratio (OR) for ORR, and relative risk (RR) for all grade and grade ≥3 TRAEs were calculated. Under Bayesian framework, the meta-analysis was conducted using sorafenib as intermediate reference.
UNASSIGNED: With the rank probability of 96%, A + A showed the greatest reduction in the risk of death, without significant difference from A + T (HR: 0.82, 95% CI: 0.65-1.04). A + T showed the greatest effect in prolonging PFS and improving ORR with the rank probability of 77%, but there were no statistical differences with A + A. A + A was safer than A + T in terms of all grade of TRAEs (RR: 0.91, 95% CI: 0.82-1.00) and particularly in those grade ≥3 (RR: 0.65, 95% CI: 0.54-0.77).
UNASSIGNED: A + A had the greatest probability of delivering the longest OS, while A + T was correlated with larger PFS benefits at the cost of a lower safety rate.
UNASSIGNED: After a rigorous literature research, 6 phase III trials were identified for the final analysis, including IMbrave150, ORIENT-32, COSMIC-312, CARES-310, LEAP-002, and REFLECT. The experiments were classified into three groups: A + A, A + T, and intermediate reference group. The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and incidence of treatment-related adverse events (TRAEs). Hazard ratio (HR) with 95% confidence intervals (CI) for OS and PFS, odds ratio (OR) for ORR, and relative risk (RR) for all grade and grade ≥3 TRAEs were calculated. Under Bayesian framework, the meta-analysis was conducted using sorafenib as intermediate reference.
UNASSIGNED: With the rank probability of 96%, A + A showed the greatest reduction in the risk of death, without significant difference from A + T (HR: 0.82, 95% CI: 0.65-1.04). A + T showed the greatest effect in prolonging PFS and improving ORR with the rank probability of 77%, but there were no statistical differences with A + A. A + A was safer than A + T in terms of all grade of TRAEs (RR: 0.91, 95% CI: 0.82-1.00) and particularly in those grade ≥3 (RR: 0.65, 95% CI: 0.54-0.77).
UNASSIGNED: A + A had the greatest probability of delivering the longest OS, while A + T was correlated with larger PFS benefits at the cost of a lower safety rate.
摘要：
■本文基于我们先前的研究，该文件在2023年ASCO年会上发表，并作为会议摘要发表在《临床肿瘤学杂志》上（JCO。2023年；41：e16148。doi：10.1200/JCO.2020.23.41.16_suppl。e16148).抗程序性死亡1/配体-1（PD-1/L1）抗体+抗血管内皮生长因子（VEGF）抗体（A+A）和抗PD-1/L1抗体+VEGF受体（VEGFR）靶向酪氨酸激酶抑制剂（A+T）是不可切除的肝细胞癌的有效一线疗法。然而,缺乏对这两种治疗方法进行正面对比的证据.我们对它们的有效性和安全性进行了网络荟萃分析。
■经过严格的文献研究，确定了6个III期试验进行最终分析，包括IMbrave150、ORIENT-32、COSMIC-312、CARES-310、LEAP-002和REFLECT。实验分为三组：A+A，A+T,和中间参考组。主要终点是总生存期（OS），次要终点包括无进展生存期（PFS），客观反应率（ORR），和治疗相关不良事件（TRAEs）的发生率。OS和PFS的风险比（HR）和95%置信区间（CI），ORR的比值比(OR)，并计算所有等级和≥3级TRAE的相对风险(RR)。在贝叶斯框架下,荟萃分析使用索拉非尼作为中间参考.
■等级概率为96%，A+A显示死亡风险降低最大，与A+T无显著差异(HR：0.82，95%CI：0.65-1.04)。A+T在延长PFS和改善ORR方面效果最大，等级概率为77%，但与A+A无统计学差异,就所有TRAE等级(RR:0.91,95%CI:0.82-1.00)而言,A+A比A+T更安全,尤其是那些等级≥3级(RR:0.65,95%CI:0.54-0.77).
■A+A最有可能提供最长的操作系统，而A+T与较高的PFS获益相关，但安全性较低。
■经过严格的文献研究，确定了6个III期试验进行最终分析，包括IMbrave150、ORIENT-32、COSMIC-312、CARES-310、LEAP-002和REFLECT。实验分为三组：A+A，A+T,和中间参考组。主要终点是总生存期（OS），次要终点包括无进展生存期（PFS），客观反应率（ORR），和治疗相关不良事件（TRAEs）的发生率。OS和PFS的风险比（HR）和95%置信区间（CI），ORR的比值比(OR)，并计算所有等级和≥3级TRAE的相对风险(RR)。在贝叶斯框架下,荟萃分析使用索拉非尼作为中间参考.
■等级概率为96%，A+A显示死亡风险降低最大，与A+T无显著差异(HR：0.82，95%CI：0.65-1.04)。A+T在延长PFS和改善ORR方面效果最大，等级概率为77%，但与A+A无统计学差异,就所有TRAE等级(RR:0.91,95%CI:0.82-1.00)而言,A+A比A+T更安全,尤其是那些等级≥3级(RR:0.65,95%CI:0.54-0.77).
■A+A最有可能提供最长的操作系统，而A+T与较高的PFS获益相关，但安全性较低。
