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.
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。
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