Department of Clinical Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, China.
Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction; Tianjin Stomatological Hospital; Hospital of Stomatology, Nankai University, China.
Biomed Res Int. 2021 Mar 13;2021:1780860. doi: 10.1155/2021/1780860. eCollection 2021.
Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer, and the majority of NSCLC patients are diagnosed at the advanced stage. Chemotherapy is still the main treatment at present, and the overall prognosis is poor. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs) as the representative have been extensively applied for treating various types of cancers. Tumor mutation burden (TMB) as a potential biomarker is used to screen appropriate patients for treatment of ICIs. To verify the predictive efficacy of TMB, a systematic review and meta-analysis were conducted to explore the association between TMB and ICIs.
PubMed, EMBASE, Cochrane Library, and son on were systematically searched from inception to April 2020. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were estimated.
A total of 11 studies consisting of 1525 nonsmall cell lung cancer (NSCLC) patients were included. Comparison of high and low TMB: pooled HRs for OS, 0.57 (95% CI 0.32 to 0.99; = 0.046); PFS, 0.48 (95% CI 0.33 to 0.69; < 0.001); ORR, 3.15 (95% CI 2.29 to 4.33; < 0.001). Subgroup analysis values: pooled HRs for OS, 0.75 (95% CI 0.29 to 1.92, = 0.548) for blood TMB (bTMB), 0.44 (95% CI 0.26 to 0.75, = 0.003) for tissue TMB (tTMB); for PFS, 0.54 (95% CI 0.29 to 0.98, = 0.044) and 0.43 (95% CI 0.26 to 0.71, = 0.001), respectively.
These findings imply that NSCLC patients with high TMB possess significant clinical benefits from ICIs compared to those with low TMB. As opposed to bTMB, tTMB was thought more appropriate for stratifying NSCLC patients for ICI treatment.
非小细胞肺癌（NSCLC）是最常见的肺癌类型，大多数 NSCLC 患者被诊断为晚期。目前化疗仍是主要治疗方法，整体预后较差。近年来，免疫治疗发展迅速。免疫检查点抑制剂（ICIs）作为代表药物，已广泛应用于多种癌症的治疗。肿瘤突变负荷（TMB）作为一种潜在的生物标志物，用于筛选合适的患者接受 ICI 治疗。为了验证 TMB 的预测疗效，进行了系统评价和荟萃分析，以探讨 TMB 与 ICI 之间的关系。
系统检索 PubMed、EMBASE、Cochrane Library 等数据库，检索时间从建库至 2020 年 4 月。评估客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
共纳入 11 项研究，包含 1525 名 NSCLC 患者。高 TMB 与低 TMB 比较：OS 的合并 HR 为 0.57（95%CI 0.32 至 0.99； = 0.046）；PFS 的合并 HR 为 0.48（95%CI 0.33 至 0.69； < 0.001）；ORR 的合并 HR 为 3.15（95%CI 2.29 至 4.33； < 0.001）。亚组分析结果：OS 的合并 HR 为 0.75（95%CI 0.29 至 1.92， = 0.548），用于血液 TMB（bTMB）；0.44（95%CI 0.26 至 0.75， = 0.003），用于组织 TMB（tTMB）；PFS 的合并 HR 为 0.54（95%CI 0.29 至 0.98， = 0.044）和 0.43（95%CI 0.26 至 0.71， = 0.001）。
这些发现表明，与低 TMB 相比，TMB 高的 NSCLC 患者从 ICI 治疗中获得了显著的临床获益。与 bTMB 相比，tTMB 更适合分层 NSCLC 患者接受 ICI 治疗。
