大panel 循环肿瘤 DNA 测序的临床实用性：国家精准医学研究中心（PRISM）研究。
Clinical utility of circulating tumor DNA sequencing with a large panel: a National Center for Precision Medicine (PRISM) study.
机构信息
Drug Development Department (DITEP) Gustave Roussy - Cancer Campus, Villejuif; Université Paris-Saclay, Faculté de médecine, Le Kremlin Bicêtre, Paris; Oncostat U1018, Inserm, Paris-Saclay University, labeled Ligue Contre le Cancer, Villejuif, France.
Drug Development Department (DITEP) Gustave Roussy - Cancer Campus, Villejuif; Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
出版信息
Ann Oncol. 2023 Apr;34(4):389-396. doi: 10.1016/j.annonc.2023.01.008. Epub 2023 Jan 25.
BACKGROUND
Circulating tumor DNA (ctDNA) sequencing is a promising approach for tailoring therapy in patients with cancer. We report hereby the results from a prospective study where we investigated the impact of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors.
PATIENTS AND METHODS
Genomic analysis was performed using the FoundationOne Liquid CDx Assay [324 genes, tumor mutational burden (TMB), microsatellite instability status]. Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were classified by ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) tier leading to molecular-based treatment suggestions wherever it was possible.
RESULTS
Between December 2020 and November 2021, 1772 patients with metastatic solid tumors underwent molecular profiling. Median time to assay results was 12 days. Results were contributive for 1658 patients (94%). At least one actionable target was detected in 1059 patients (64%) with a total of 1825 actionable alterations including alteration of the DNA damage repair response pathway (n = 336, 18%), high TMB (>16 mutations/Mb; n = 243, 13%), PIK3CA mutations (n = 150, 8%), ERBB family pathway alterations (n = 127, 7%), PTEN alterations (n = 95, 5%), FGFR alterations (n = 67, 4%) and MET activations (n = 13, 0.7%). The MTB recommended a matched therapy for 597 patients (56%) with a total of 819 therapeutic orientations: clinical trials (n = 639, 78%), off-label/compassionate use (n = 81, 10%), approved drug (n = 51, 6%), and early access program (n = 48, 6%). In total, 122 patients (21%) were treated. Among the assessable patients (n = 107), 4 (4%) had complete response, 35 (33%) had partial response, 27 (25%) had stable disease, and 41 (38%) a progressive disease as best response. The median progression-free survival and median overall survival were 4.7 months (95% confidence interval 2.7-6.7 months) and 8.3 months (95% confidence interval 4.7-11.9 months) respectively.
CONCLUSIONS
ctDNA sequencing with a large panel is an efficient approach to match patients with advanced cancer with targeted therapies.
背景
循环肿瘤 DNA（ctDNA）测序是一种针对癌症患者进行精准治疗的有前途的方法。我们在此报告一项前瞻性研究的结果，该研究调查了对晚期实体瘤患者进行 ctDNA 全面分子谱分析的影响。
患者和方法
使用 FoundationOne Liquid CDx 检测试剂盒（324 个基因、肿瘤突变负荷（TMB）、微卫星不稳定性状态）进行基因组分析。每个单独的基因组报告都由多学科肿瘤委员会（MTB）每周进行审查和讨论。根据 ESMO 分子靶向治疗临床可操作性量表（ESCAT）的分层，对可操作的靶点进行分类，只要有可能，就会提出基于分子的治疗建议。
结果
在 2020 年 12 月至 2021 年 11 月期间，1772 名转移性实体瘤患者接受了分子谱分析。检测结果的中位时间为 12 天。1658 名患者（94%）的结果具有可评估性。1059 名患者（64%）中至少检测到一个可操作的靶点，共检测到 1825 个可操作的改变，包括 DNA 损伤修复反应途径的改变（n=336，18%）、高 TMB（>16 个突变/Mb；n=243，13%）、PIK3CA 突变（n=150，8%）、ERBB 家族途径改变（n=127，7%）、PTEN 改变（n=95，5%）、FGFR 改变（n=67，4%）和 MET 激活（n=13，0.7%）。MTB 建议对 597 名患者（56%）进行匹配治疗，共有 819 种治疗方向：临床试验（n=639，78%）、无标签/同情用药（n=81，10%）、批准药物（n=51，6%）和早期准入计划（n=48，6%）。共有 122 名患者（21%）接受了治疗。在可评估患者（n=107）中，4 名（4%）患者完全缓解，35 名（33%）患者部分缓解，27 名（25%）患者疾病稳定，41 名（38%）患者疾病进展。无进展生存期和总生存期的中位数分别为 4.7 个月（95%置信区间为 2.7-6.7 个月）和 8.3 个月（95%置信区间为 4.7-11.9 个月）。
结论
使用大panel 对 ctDNA 进行测序是一种有效的方法，可以将晚期癌症患者与靶向治疗相匹配。
Zotero 插件