The Cancer Genome Atlas Expression Subtypes Stratify Response to Checkpoint Inhibition in Advanced Urothelial Cancer and Identify a Subset of Patients with High Survival Probability
The Cancer Genome Atlas Expression Subtypes Stratify Response to Checkpoint Inhibition in Advanced Urothelial Cancer and Identify a Subset of Patients with High Survival Probability
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DOI：
10.1016/j.eururo.2019.02.017
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发表时间：
2019-06-01
期刊：
影响因子：
23.4
通讯作者：
Lerner, Seth P.
中科院分区：
文献类型：
--
作者：
Kim, Jaegil;Kwiatkowski, David;Lerner, Seth P.
对IMvigor 210试验的分析涉及接受PD-L1抑制剂atezolizumab治疗的铂类难治性或不适合顺铂的尿路上皮癌患者，发现耐药特征是一种免疫生物标志物。来自该试验的368个肿瘤样本的转录组分析显示，“基因组不稳定”的隆德亚型分类与最佳缓解相关。我们开发并应用了一种基于癌症基因组图谱2017表达的分子亚型的新型单患者亚型分类器。我们确定了11例神经元亚型患者，其中8例确诊病例的缓解率为100%（2例完全缓解，6例部分缓解），总体缓解率为72%，包括3/11例未确认缓解的患者。生存概率是非常高的神经元亚型，这是一个高风险的队列与先进的疾病，并可能是继发于低水平的TGF β表达和高突变/neoantigen burden.Patient摘要：我们描述了一种方法，基因组分类的个体患者的膀胱癌肿瘤，并确定了一个亚型，是与免疫治疗的高反应率。这是为正确的患者确定正确治疗方法的重要一步，这是个性化精准医疗的目标。(C)2019年欧洲泌尿外科协会。Elsevier B. V.出版，保留所有权利。
Analysis of the IMvigor 210 trials involving patients with platinum-refractory or cisplatin-ineligible urothelial carcinoma who were treated with the PD-L1 inhibitor atezolizumab identified a resistance signature as an immune biomarker. Transcriptome profiling of 368 tumor samples from this trial revealed that the "genomically unstable" Lund subtype classification was associated with the best response. We developed and applied a novel single-patient subtype classifier based on The Cancer Genome Atlas 2017 expression-based molecular subtypes. We identified 11 patients with a neuronal subtype, with a 100% response rate in eight confirmed cases (2 complete response, 6 partial response), and 72% overall, including 3/11 patients with an unconfirmed response. The survival probability was extraordinarily high for the neuronal subtype, which represents a high-risk cohort with advanced disease, and may be secondary to low levels of TGF beta expression and high mutation/neoantigen burden.Patient summary: We describe a methodology for genomic classification of an individual patient's bladder cancer tumor and have identified a subtype that is associated with a high response rate to immunotherapy. This is an important step forward in identifying the right treatment for the right patient, which is the goal of personalized precision medicine. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.