晚期非小细胞肺癌中疗效与 PD-1/PD-L1 抑制和肿瘤突变负担的关联：一项基于 PRISMA 的文献回顾和荟萃分析。

The association of efficacy with PD-1/PD-L1 inhibition and tumor mutational burden in advanced nonsmall cell lung cancer: A PRISMA-guided literature review and meta-analysis.

机构信息

Department of Cardiothoracic Surgery, Yuyao People's Hospital, Yuyao 315400, Zhejiang Province, China.

出版信息

Medicine (Baltimore). 2022 Jul 22;101(29):e29676. doi: 10.1097/MD.0000000000029676.

BACKGROUND

Tumor mutation burden (TMB) has been reported to emerge as an independent biomarker of response to identify patients who would achieve benefit from immune checkpoint inhibitors. However, it still remains controversy that whether TMB can be a robust biomarker of response to programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibition. We performed this meta-analysis to assess the relationship between TMB and the efficacy with PD-1/PD-L1 inhibition in advanced nonsmall cell lung cancer (NSCLC).

METHODS

Following the recommendations of the PRISMA statement, electronic databases literature search was done on the published articles till March 2021, including Pubmed, Embase, and Cochrane library databases. Studies were selected that focused on comparing the efficacy of TMB-high group and TMB-low group in NSCLC patients received with immune checkpoint inhibitors. Meta-analysis Revman 5.3 software was utilized to calculate the pooled outcomes.

RESULTS

A systematic literature search was conducted 8 articles, including 11 comparative articles. Findings of our studies shown that patients with TMB-high group was associated with better clinical outcomes than TMB-low group, including progression-free survival (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.29-0.49; P < .00001), complete response (OR, 4.71; 95% CI, 2.32-9.57; P < .0001), durable clinical benefit (OR, 3.76; 95% CI, 2.38-5.96; P < .00001) and the objective response rate (OR, 3.14; 95% CI, 1.83-5.37; P < .0001). While, it failed to predict overall survival benefits (OR, 0.74; 95% CI, 0.45-1.20; P = .22).

CONCLUSIONS

Our study found that NSCLC with high TMB who benefit from immunotherapy. The findings suggest that TMB could associated with a greater predictive power of response. Possibly a more TMB-oriented prediction model might gain more benefits from PD-1/PD-L1 inhibitors.

背景

肿瘤突变负担（TMB）已被报道为一种独立的生物标志物，可用于识别可能从免疫检查点抑制剂中获益的患者。然而，TMB 是否可以作为程序性死亡受体-1（PD-1）/程序性死亡配体 1（PD-L1）抑制剂反应的有力生物标志物仍存在争议。我们进行了这项荟萃分析，以评估 TMB 与晚期非小细胞肺癌（NSCLC）患者接受 PD-1/PD-L1 抑制治疗的疗效之间的关系。

方法

根据 PRISMA 声明的建议，对截至 2021 年 3 月发表的文献进行了电子数据库文献检索，包括 Pubmed、Embase 和 Cochrane 图书馆数据库。选择了重点比较 TMB 高组和 TMB 低组 NSCLC 患者接受免疫检查点抑制剂治疗疗效的研究。使用 Meta-analysis Revman 5.3 软件计算汇总结果。

结果

系统文献检索共 8 篇文章，包括 11 篇比较性文章。我们的研究结果表明，TMB 高组患者的临床结局优于 TMB 低组患者，包括无进展生存期（优势比 [OR]，0.38；95%置信区间 [CI]，0.29-0.49；P<0.00001）、完全缓解（OR，4.71；95%CI，2.32-9.57；P<0.0001）、持久临床获益（OR，3.76；95%CI，2.38-5.96；P<0.00001）和客观缓解率（OR，3.14；95%CI，1.83-5.37；P<0.0001）。然而，它未能预测总体生存获益（OR，0.74；95%CI，0.45-1.20；P=0.22）。