Clinical significance of tumour mutation burden in immunotherapy across multiple cancer types: an individual meta-analysis
Clinical significance of tumour mutation burden in immunotherapy across multiple cancer types: an individual meta-analysis
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多种癌症类型免疫治疗中肿瘤突变负担的临床意义：个体荟萃分析
DOI：
10.1093/jjco/hyaa076
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发表时间：
2020-09-01
影响因子：
2.4
通讯作者：
Liu, Lunxu
中科院分区：
文献类型：
--
作者：
Yang, Zhenyu;Wei, Shiyou;Liu, Lunxu
背景：用于对可受益于免疫检查点抑制剂的患者进行分层的生物标志物是必要的。肿瘤突变负荷最近已成为癌症中一种有前景的生物标志物，但目前的研究中尚未充分记录肿瘤突变负荷与免疫检查点抑制剂治疗结果之间的关联。方法：我们检索了截至 2019 年 10 月 1 日的 PubMed、Web of Science 和 EMBASE 数据库。纳入了评估肿瘤突变负荷与临床结果之间关联的研究。应用风险比和比值比分别估计肿瘤突变负荷评分与总生存期、无进展生存期和缓解率的关联。最佳截止值是通过使用 Contal 和 O'Quigley 方法进行最佳区分的总生存期来选择的。结果：纳入了涉及 6171 名不同癌症患者的 22 项研究。个体参与者数据荟萃分析表明，高肿瘤突变负荷与更好的总生存期（HR = 0.57，95% CI = 0.50-0.64）和无进展生存期（HR = 0.50，95% CI = 0.40-0.63）和更高的缓解率相关。每种癌症类型的最佳截止值分别为：非小细胞肺癌 17.7/MB、膀胱癌 7.9/MB、黑色素瘤 6.1/MB、结直肠癌 12.3/MB、食管胃癌 6.9/MB、头颈癌 10.5/MB。汇总荟萃分析显示预后价值稳健，预测缓解率的敏感性、特异性和受试者工作特征曲线下面积分别为 0.63、0.71 和 0.73。 结论：本荟萃分析表明肿瘤突变负荷是免疫检查点抑制剂治疗的一个有希望的预测因子，但不同癌症的截止值不同。
Background: Biomarkers for stratifying patients that could benefit from immune checkpoint inhibitors are necessary. Tumour mutation burden has recently become a promising biomarker in cancer, but the associations between tumour mutation burden and outcomes of immune checkpoint inhibitors treatment were not well-documented in present studies.Methods: We searched PubMed, Web of Science and EMBASE databases up to 1 October 2019. Studies evaluated the association between tumour mutation burden and clinical outcomes were included. Hazard ratios and odds ratios were applied to estimate the association of tumour mutation burden score with overall survival, progression-free survival and response rate, respectively. The best cut-off value was chosen by best discriminated overall survival using Contal and O'Quigley method.Results: Twenty-two studies involving 6171 patients in diverse cancers were included. The individual participant data meta-analysis demonstrated that high tumour mutation burden was associated with better overall survival (HR = 0.57, 95% CI = 0.50-0.64) and progression-free survival (HR = 0.50, 95% CI = 0.40-0.63) and higher response rate. The best cut-off values in each cancer type were 17.7/MB in non-small cell lung cancer, 7.9/MB in bladder cancer, 6.1/MB in melanoma, 12.3/MB in colorectal cancer, 6.9/MB in esophagogastric cancer, 10.5/MB in head and neck cancer. The pooled meta-analysis showed the prognosis value was robust and the sensitivity, specificity and area under the receiver operating characteristic curves in predicting response rates were 0.63, 0.71 and 0.73, respectively.Conclusions: The present meta-analysis indicates tumour mutation burden is a promising predictor of immune checkpoint inhibitors therapy but the cut-off value differs in different cancers.