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.
■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。