High tumor mutation burden predicts better efficacy of immunotherapy: a pooled analysis of 103078 cancer patients
High tumor mutation burden predicts better efficacy of immunotherapy: a pooled analysis of 103078 cancer patients
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高肿瘤突变负荷预示免疫治疗效果更好：对 103078 名癌症患者的汇总分析
DOI：
10.1080/2162402x.2019.1629258
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发表时间：
2019-06-17
期刊：
影响因子：
7.2
通讯作者：
Ge, Wei
中科院分区：
文献类型：
--
作者：
Cao, Dedong;Xu, Huilin;Ge, Wei
摘要肿瘤突变负荷（TMB）和接受免疫治疗的癌症患者的结果之间的关系已被报道。本研究旨在评估TMB在接受免疫治疗的癌症患者中的预后作用。系统性检索了Embase、PubMed和科克伦图书馆等数据库，以确定截至2018年9月的潜在合格研究，无语言限制。选择了评估高TMB与低TMB在预测各种癌症患者存活率方面的研究。使用高TMB与低TMB的总生存期（OS）和无进展生存期（PFS）的风险比（HR）以及总缓解率（ORR）的比值比（OR）进行汇总分析。主要终点为OS，次要终点为PFS和ORR。共纳入45项研究，包括103078例癌症患者。综合结果显示，当用免疫疗法治疗时，高TMB与更好的OS（HR = 0.40; 95%置信区间（CI）：0.30-0.53; p< .00001）、PFS（HR = 0.37; 95%CI：0.26-0.53; p< .00001）和ORR（OR = 4.62; 95%CI：2.90-7.34; p< .0001）相关。在研究高TMB患者时，当比较免疫治疗与化疗时，这些患者的OS有所改善（HR = 0.69; 95%CI：0.47-1.03; p= 0.07）。亚组分析表明，TMB的预后作用与癌症类型和TMB检测方法无关（所有p<0.05）。我们的研究结果表明，高TMB与接受免疫治疗的癌症患者的生存率更高相关。对于TMB高的癌症患者，可以考虑免疫治疗。
ABSTRACT The relation between tumor mutation burden (TMB) and outcome of cancer patients receiving immunotherapy has been reported. This study aimed to evaluate the prognostic role of TMB in cancer patients receiving immunotherapy. Databases including Embase, PubMed, and the Cochrane library were systematically searched to identify potentially eligible studies until Sep 2018 without language limitation. Studies assessing high versus low TMB in predicting survival of various cancer patients were selected. The pooled analyses were conducted using hazard ratio (HR) of high versus low TMB for overall survival (OS) and progression-free survival (PFS), and the odds ratio (OR) for overall response rate (ORR). The primary endpoint was OS. Secondary outcomes were PFS and ORR. A total of 45 studies consisting of 103078 cancer patients were included. The combined results showed that high TMB was associated with better OS (HR = 0.40; 95% confidence interval (CI):0.30–0.53; p< .00001), PFS (HR = 0.37; 95% CI: 0.26–0.53; p< .00001) and ORR (OR = 4.62; 95%CI: 2.90–7.34; p< .0001) when treated with immunotherapy. In studying patients with high TMB, these patients had improved OS (HR = 0.69; 95%CI: 0.47–1.03; p= .07) when comparing immunotherapy to chemotherapy. Subgroup analyses suggested that the prognostic role of TMB was independent of cancer types and TMB detection methods (all p< .05). Our findings suggest that high TMB is associated with better survival in cancer patients receiving immunotherapy. For cancer patients with high TMB, immunotherapy could be considered.