Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab
Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab
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DOI：
10.1038/s43018-020-0096-5
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发表时间：
2020-09-01
期刊：
影响因子：
22.7
通讯作者：
Pugh, Trevor J.
中科院分区：
文献类型：
--
作者：
Bratman, Scott V.;Yang, S. Y. Cindy;Pugh, Trevor J.
免疫检查点阻断 (ICB) 为一部分癌症患者提供临床益处。然而，现有的生物标志物并不能可靠地预测不同癌症类型的治疗反应。目前有限的数据表明连续循环肿瘤 DNA (ctDNA) 检测如何作为接受 ICB 的患者的预测生物标志物。我们进行了一项前瞻性 II 期临床试验，以评估五个不同队列的接受派姆单抗治疗的晚期实体瘤患者的 ctDNA (NCT02644369)。我们对 94 名患者在基线和每三个周期获得的 316 个系列血浆样本进行了定制 ctDNA 检测。基线 ctDNA 浓度与无进展生存期、总生存期、临床反应和临床获益相关。当考虑治疗期间的 ctDNA 动力学时，这种关联变得更强。治疗期间 ctDNA 清除的所有 12 名患者在中位随访 25 个月后均存活。这项研究证明了基于 ctDNA 的监测在 ICB 治疗患者中具有广泛的临床应用潜力。 Siu 及其同事使用定制的 ctDNA 检测，并在接受派姆单抗（包括多种实体瘤类型）的患者的 II 期临床试验中显示了纵向 ctDNA 分析的预测效用。
Immune checkpoint blockade (ICB) provides clinical benefit to a subset of patients with cancer. However, existing biomarkers do not reliably predict treatment response across diverse cancer types. Limited data exist to show how serial circulating tumor DNA (ctDNA) testing may perform as a predictive biomarker in patients receiving ICB. We conducted a prospective phase II clinical trial to assess ctDNA in five distinct cohorts of patients with advanced solid tumors treated with pembrolizumab (NCT02644369). We applied bespoke ctDNA assays to 316 serial plasma samples obtained at baseline and every three cycles from 94 patients. Baseline ctDNA concentration correlated with progression-free survival, overall survival, clinical response and clinical benefit. This association became stronger when considering ctDNA kinetics during treatment. All 12 patients with ctDNA clearance during treatment were alive with median 25months follow up. This study demonstrates the potential for broad clinical utility of ctDNA-based surveillance in patients treated with ICB. Siu and colleagues use a bespoke ctDNA assay and show predictive utility of longitudinal ctDNA analysis in a phase II clinical trial of patients receiving pembrolizumab that included multiple solid tumor types.