Abstract:
The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway plays a crucial role in the immune escape mechanism and growth of cancer cells in endometrial cancer (EC). Clinical trials investigating PD-1/PD-L1 inhibitor have shown promising results in other cancers, but their efficacy in EC still remains uncertain. Therefore, this meta-analysis aims to provide an updated and robust analysis of the effectiveness and safety of PD-1/PDL1 inhibitor as single-agent immunotherapy in EC, focusing on the objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). This meta-analysis utilized STATA version 17 and RevMan version 5.4 software to pool the results of relevant studies. Five studies conducted between 2017 and 2022, comprising a total of 480 EC patients enrolled for PD-1/PD-L1 inhibitor immunotherapy met the inclusion criteria. The pooled proportion of EC patients who achieved ORR through PD-1/PD-L1 inhibitor treatment was 26.0% (95% CI: 16.0-36.0%; p < 0.05). Subgroup analysis based on mismatch repair (MMR) status showed an ORR of 44.0% (95% CI: 38.0-50.0%; p = 0.32) for the deficient mismatch repair (dMMR) group and 8.0% (95% CI: 0.0-16.0%; p = 0.07) for the proficient mismatch repair (pMMR) group. Pooled proportion analysis by DCR demonstrated an odds ratio (OR) of 41.0% (95% CI: 36.0-46.0%, p = 0.83) for patients undergoing PD-1/PD-L1 inhibitor treatment. Subgroup analysis based on MMR status revealed DCR of 54.0% (95% CI: 47.0-62.0%; p = 0.83) for the dMMR group, and 31.0% (95% CI: 25.0-39.0%; p = 0.14) for the pMMR group. The efficacy of PD-1/PD-L1 inhibitors was significantly higher in the dMMR group compared to the pMMR group, in terms of both ORR (OR = 6.30; 95% CI = 3.60-11.03; p < 0.05) and DCR (OR = 2.57; 95% CI = 1.66-3.99; p < 0.05). In terms of safety issues, the pooled proportion of patients experiencing at least one adverse event was 69.0% (95% CI: 65.0-73.0%; p > 0.05), with grade three or higher AEs occurring in 16.0% of cases (95% CI: 12.0-19.0%; p > 0.05). Based on the subgroup analysis of MMR status, PD-1/PD-L1 inhibitor immunotherapy showed significantly better efficacy among dMMR patients. These findings suggest that patients with dMMR status may be more suitable for this treatment approach. However, further research on PD-1/PD-L1 inhibitor immunotherapy strategies is needed to fully explore their potential and improve treatment outcomes in EC.
摘要:
程序性细胞死亡蛋白1(PD-1)/程序性细胞死亡配体1(PD-L1)通路在子宫内膜癌(EC)的免疫逃逸机制和癌细胞的生长中起着至关重要的作用。研究PD-1/PD-L1抑制剂的临床试验在其他癌症中显示出有希望的结果,但其在EC中的疗效仍不确定。因此,这项荟萃分析旨在提供对PD-1/PDL1抑制剂作为EC单药免疫治疗的有效性和安全性的最新和可靠的分析,关注客观反应率(ORR),疾病控制率(DCR),和不良事件(AE)。该荟萃分析使用STATA版本17和RevMan版本5.4软件汇集了相关研究的结果。2017年至2022年进行的五项研究,包括480名接受PD-1/PD-L1抑制剂免疫治疗的EC患者符合纳入标准。通过PD-1/PD-L1抑制剂治疗达到ORR的EC患者的合并比例为26.0%(95%CI:16.0-36.0%;p<0.05)。基于错配修复(MMR)状态的亚组分析显示,缺陷错配修复(dMMR)组的ORR为44.0%(95%CI:38.0-50.0%;p=0.32),而熟练错配修复(pMMR)组的ORR为8.0%(95%CI:0.0-16.0%;p=0.07)。DCR汇总比例分析显示比值比(OR)为41.0%(95%CI:36.0-46.0%,p=0.83),适用于接受PD-1/PD-L1抑制剂治疗的患者。基于MMR状态的亚组分析显示dMMR组的DCR为54.0%(95%CI:47.0-62.0%;p=0.83),pMMR组为31.0%(95%CI:25.0-39.0%;p=0.14)。dMMR组PD-1/PD-L1抑制剂的疗效明显高于pMMR组,ORR(OR=6.30;95%CI=3.60-11.03;p<0.05)和DCR(OR=2.57;95%CI=1.66-3.99;p<0.05)。在安全问题上,发生至少一次不良事件的患者的合并比例为69.0%(95%CI:65.0-73.0%;p>0.05),在16.0%的病例中发生3级或更高的AE(95%CI:12.0-19.0%;p>0.05)。基于MMR状态的子群分析,PD-1/PD-L1抑制剂免疫治疗在dMMR患者中显示出明显更好的疗效。这些发现表明,具有dMMR状态的患者可能更适合这种治疗方法。然而,需要进一步研究PD-1/PD-L1抑制剂免疫治疗策略,以充分发掘其潜力并改善EC治疗结局.