新型冠状病毒性肺炎症状有哪些

JCO:这两个因素是预测免疫检查点抑制剂治疗肺癌是否有效的关键

JCO:这两个因素是预测免疫检查点抑制剂治疗<a href=http://www.bdxfy.com/feiai>肺癌</a>是否有效的关键” inline=”0″></p>
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《临床肿瘤学杂志》2018年1月16日在线先发

在靶向二代测序的非小细胞肺癌患者中反应阻断抗程序性细胞死亡(PD-1和抗程序性死亡配体(PD-L-1疗效的关键分子

目的

免疫检查点抑制剂(ICIs)治疗晚期非小细胞肺癌在亚组患者中疗效持久、生存期延长。临床上需要有用于优化使用免疫检测点抑制剂的手段和了解治疗反应关键分子的工具。靶向二代测序(NGS)越来越普遍,但其在识别免疫检查点抑制剂治疗反应预测方面的作用尚不清楚。

方法

对用抗程序性死亡1或抗程序性死亡配体1[抗程序性细胞死亡(PD)-1]治疗的且进行了靶向二代测序的晚期非小细胞肺癌患者(MSK-IMPACT,n=240),收集详尽的临床资料及治疗反应数据。通过“实体瘤疗效评价标准(RECIST)1.1版本”评价疗效,持续临床获益(DCB)的界定为部分缓解/疾病稳定时间持续>6个月。在持续临床获益和没有持续获益(NDB)的患者中,对肿瘤突变负荷(TMB)、拷贝数有变化的基因比例和基因改变情况进行了比较。对49例患者进行了全外显子测序(WES),以比较靶向二代测序对比全外显子测序所测得的肿瘤突变负荷量。

结果

通过靶向二代测序测得的肿瘤突变负荷量与通过全外显子测序测得的肿瘤突变负荷量相关性好(P=0.86,P<0.001)。持续临床获益患者比没有持续获益患者的肿瘤突变负荷大(P=0.006)。在肿瘤突变负荷上50百分位对比下50百分位的患者中,随着肿瘤突变负荷阈值的增加,持续临床缓解更常见、无进展生存期更长(38.6%对比25.1%,P<0.001;风险比1.38,P=0.024)。在没有持续获益患者中,拷贝数有变化的基因的比例最高。EGFR和STK11变异与不获益相关。肿瘤突变负荷和PD-L1表达是独立变量,且肿瘤突变负荷+PD-L1进一步增加了对免疫检查点抑制剂的获益。

结论

靶向二代测序可以准确估算肿瘤突变负荷,且升高的肿瘤突变负荷进一步增加了对免疫检查点抑制剂获益的可能性。肿瘤突变负荷与PD-L1表达没有关系,这两个变量有相近的预测能力。在多变量预测模型中同时加入肿瘤突变负荷和PD-L1表达会产生更好的预测能力。

《壹篇》孙莉

JCO:这两个因素是预测免疫检查点抑制剂治疗肺癌是否有效的关键

JCO:这两个因素是预测免疫检查点抑制剂治疗肺癌是否有效的关键

JCO:这两个因素是预测免疫检查点抑制剂治疗肺癌是否有效的关键

JCO:这两个因素是预测免疫检查点抑制剂治疗肺癌是否有效的关键

http://ascopubs.org/doi/full/10.1200/JCO.2017.75.3384

Molecular Determinants of Response to Anti–Programmed Cell Death (PD)-1 and Anti–Programmed Death-Ligand (PD-L)-Ligand 1 Blockade in Patients With Non–Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing

Purpose

Treatment of advanced non–small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known.

Methods

Detailed clinical annotation and response data were collected for patients with advanced non–small-cell lung cancer treated with anti–programmed death-1 or anti–programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240). Efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and durable clinical benefit (DCB) was defined as partial response/stable disease that lasted > 6 months. Tumor mutation burden (TMB), fraction of copy number–altered genome, and gene alterations were compared among patients with DCB and no durable benefit (NDB). Whole-exome sequencing (WES) was performed for 49 patients to compare quantification of TMB by targeted NGS versus WES.

Results

Estimates of TMB by targeted NGS correlated well with WES (ρ = 0.86; P < .001). TMB was greater in patients with DCB than with NDB (P = .006). DCB was more common, and progression-free survival was longer in patients at increasing thresholds above versus below the 50th percentile of TMB (38.6% v 25.1%; P < .001; hazard ratio, 1.38; P = .024). The fraction of copy number–altered genome was highest in those with NDB. Variants in EGFR and STK11 associated with a lack of benefit. TMB and PD-L1 expression were independent variables, and a composite of TMB plus PD-L1 further enriched for benefit to ICIs.

Conclusion

Targeted NGS accurately estimates TMB and elevated TMB further improved likelihood of benefit to ICIs. TMB did not correlate with PD-L1 expression; both variables had similar predictive capacity. The incorporation of both TMB and PD-L1 expression into multivariable predictive models should result in greater predictive power.

JCO:这两个因素是预测免疫检查点抑制剂治疗肺癌是否有效的关键

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