目的:探讨程序性细胞死亡1(PD-1)/程序性细胞死亡配体1(PD-L1)联合细胞毒性T淋巴细胞抗原-4(CTLA-4)抗体±其他治疗晚期肺癌的疗效和安全性。
方法:根据检索策略,我们在电子数据库中搜索了肺癌患者PD-1/PD-L1加CTLA-4抗体的随机对照试验;RR(用于客观缓解率(ORR),总生存期(OS),无进展生存期(PFS),和免疫相关的不良事件(irAE))来自个别研究的计算和汇总使用随机效应模型或固定效应模型;异质性和发表偏倚分析也进行了,使用ReviewManager5.3和Stata15.1进行统计分析。
结果:我们纳入了6项研究。四种不同的免疫检查点抑制剂(nivolumab,pembrolizumab,durvalumab,使用tremelimumab)。双重检查点抑制剂±其他疗法治疗晚期肺癌的ORR显着改善(RR1.49,95%CI1.11至1.98;p=0.007),OS(HR0.72,95%CI0.63至0.83;p<0.00001),和PFS(HR0.72,95%CI0.63至0.82;p<0.00001)。亚组分析与合并结果一致。PD-L1≥1%(HR0.67,95%CI0.54至0.82;p<0.0001)亚组差异表明有统计学意义的亚组效应,但PD-L1<1%亚组(HR0.88,95%CI0.75~1.05;p=0.15)无统计学意义.不良事件发生率(≥3级)低于对照组(RR0.90,95%CI0.80至1.02;p=0.09),但并不重要。
结论:PD-1/PD-L1抑制剂联合CTLA-4抑制剂±其他疗法可改善ORR,晚期或转移性肺癌患者的OS和PFS,但不良反应发生率较高,虽然一般可以耐受。
未经评估:CRD42020149216。
To investigate the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) plus cytotoxic T lymphocyte antigen-4 (CTLA-4) antibodies ± other therapies in patients with advanced lung cancer.
In accordance with the retrieval strategy, we searched electronic databases for randomised controlled trials testing PD-1/PD-L1 plus CTLA-4 antibodies in patients with lung cancer; RR (for objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs)) from individual studies were calculated and pooled by using random-effects models or fixed-effects models; heterogeneity and publication bias analyses were also performed, using
Review Manager 5.3 and Stata 15.1 for statistical analysis.
We included six studies. Four different immune checkpoint inhibitors (nivolumab, pembrolizumab, durvalumab, tremelimumab) were used. Dual checkpoint inhibitors ± other therapies for advanced lung cancer showed significant improvements in ORR (RR 1.49, 95% CI 1.11 to 1.98; p=0.007), OS (HR 0.72, 95% CI 0.63 to 0.83; p<0.00001), and PFS (HR 0.72, 95% CI 0.63 to 0.82; p<0.00001). The subgroup analyses were consistent with the pooled results. The PD-L1 ≥1% (HR 0.67, 95% CI 0.54 to 0.82; p<0.0001) subgroup differences indicated a statistically significant subgroup effect, but the PD-L1 <1% subgroup (HR 0.88, 95% CI 0.75 to 1.05; p=0.15) was not statistically significant. The incidence of adverse events (grade ≥3) was lower than that of the control group (RR 0.90, 95% CI 0.80 to 1.02; p=0.09), but was not significant.
PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors ± other therapies can improve the ORR, OS and PFS of patients with advanced or metastatic lung cancer, but the incidence of adverse reactions is high although generally tolerable.
CRD42020149216.