基于血液的肿瘤突变负担水平与 PD-1/PD-L1 抑制剂在晚期非小细胞肺癌中的疗效关系：系统评价和荟萃分析。

The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis.

机构信息

Department of Integrated Traditional and Western Medicine in Oncology, First Affiliated Hospital of Medical University of Anhui, Anhui, China.

Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical University of Anhui, Anhui, China.

出版信息

BMC Cancer. 2021 Nov 13;21(1):1220. doi: 10.1186/s12885-021-08924-z.

DOI:10.1186/s12885-021-08924-z

PMID:34774004

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8590772/

Abstract

BACKGROUND

The predictive role of blood-based tumor mutation burden (bTMB) for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate. Therefore, the purpose of this meta-analysis was to evaluate the efficacy of programmed cell death 1 (PD-1) /programmed cell death ligand 1 (PD-L1) inhibitors versus that of standard-of-care therapy in patients with NSCLC who were bTMB high and bTMB low.

METHODS

PubMed, Embase, Cochrane, the Web of Science, and ClinicalTrials.gov were searched systematically from inception to February 2021 for studies of PD-1/PD-L1 inhibitors (durvalumab OR atezolizumab OR avelumab OR pembrolizumab OR Nivolumab) that provided hazard ratios (HRs) for overall survival (OS) or progression-free survival (PFS), or odds ratios (ORs) for objective response rate (ORR) in both bTMB high and bTMB low groups.

RESULTS

A total of 2338 patients with advanced or metastatic NSCLC from six randomized controlled trials, which all used chemotherapy (CT) as a control, were included in this study. Compared with CT, PD-1/PD-L1 inhibitor therapy improved OS (HR 0.62, 95% CI 0.52-0.75, P < 0.01), PFS (HR 0.57, 95% CI 0.48-0.67, P < 0.01), and ORR (OR 2.69, 95% CI 1.84-3.93, P < 0.01) in bTMB-high NSCLC patients but not in bTMB-low patients (OS HR 0.86, 95% CI 0.69-1.07, P = 0.17; PFS HR 1.00, 95% CI 0.78-1.27, P = 0.98; ORR OR 0.63, 95% CI 0.49-0.80, P = 0.03). Subgroup analyses showed that these results were consistent across all subgroups (line of therapy, therapy regimen, type of NGS panel, PD-L1 expression, and cutoff value). Meta-regression analysis showed that the proportion of patients with squamous cell histology had no statistical effect on clinical outcomes. Sensitivity analyses illustrated that all results were stable.

CONCLUSIONS

The efficacy of PD-1/PD-L1 inhibitor therapy in advanced NSCLC patients may be dependent on bTMB level. Patients with high bTMB tend to obtain significantly better OS, PFS, and ORR from PD-1/PD-L1 inhibitor therapy than from CT. However, because of multiple limitations, including those related to reproducibility, the results are exploratory and should be interpreted with caution.

摘要

背景

血液肿瘤突变负荷（bTMB）对选择可能从免疫检查点抑制剂（ICI）中获益的晚期非小细胞肺癌（NSCLC）患者的预测作用仍存在争议。因此，本荟萃分析的目的是评估程序性细胞死亡蛋白 1（PD-1）/程序性死亡配体 1（PD-L1）抑制剂与标准治疗相比，在 bTMB 高和 bTMB 低的 NSCLC 患者中的疗效。

方法

系统检索 PubMed、Embase、Cochrane、Web of Science 和 ClinicalTrials.gov，从成立到 2021 年 2 月，以获取 PD-1/PD-L1 抑制剂（度伐利尤单抗或阿替利珠单抗或avelumab 或 pembrolizumab 或纳武利尤单抗）的研究，这些研究提供了总体生存（OS）或无进展生存（PFS）的风险比（HR），或客观缓解率（ORR）的比值比（OR），分别在 bTMB 高和 bTMB 低组。

结果

共有 2338 名来自六项随机对照试验的晚期或转移性 NSCLC 患者纳入本研究，所有试验均采用化疗（CT）作为对照。与 CT 相比，PD-1/PD-L1 抑制剂治疗改善了 bTMB 高 NSCLC 患者的 OS（HR 0.62，95%CI 0.52-0.75，P<0.01）、PFS（HR 0.57，95%CI 0.48-0.67，P<0.01）和 ORR（OR 2.69，95%CI 1.84-3.93，P<0.01），但在 bTMB 低患者中则不然（OS HR 0.86，95%CI 0.69-1.07，P=0.17；PFS HR 1.00，95%CI 0.78-1.27，P=0.98；ORR OR 0.63，95%CI 0.49-0.80，P=0.03）。亚组分析显示，这些结果在所有亚组中均一致（治疗线、治疗方案、NGS 面板类型、PD-L1 表达和截止值）。Meta 回归分析显示，鳞状细胞组织学患者的比例对临床结局没有统计学影响。敏感性分析表明，所有结果均稳定。