全面的游离循环肿瘤 DNA 与标准护理组织检测在晚期非小细胞肺癌中的生物标志物发现和结果。
Biomarker Discovery and Outcomes for Comprehensive Cell-Free Circulating Tumor DNA Versus Standard-of-Care Tissue Testing in Advanced Non-Small-Cell Lung Cancer.
机构信息
ICO Bellvitge, Hospitalet Llobregat/Spain.
Hospital del Mar, Barcelona, Spain.
出版信息
JCO Precis Oncol. 2021 Nov;5:93-102. doi: 10.1200/PO.20.00241.
PURPOSE
Treatment guidelines for advanced non-small-cell lung cancer (aNSCLC) recommend broad molecular profiling for targeted therapy selection. This study prospectively assessed comprehensive next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) compared with standard-of-care (SOC) tissue-based testing to identify guideline-recommended alterations in aNSCLC.
PATIENTS AND METHODS
Patients with treatment-naïve aNSCLC were tested using a well-validated NGS cfDNA panel, and results were compared with SOC tissue testing. The primary objective was noninferiority of cfDNA vs. tissue analysis for the detection of two guideline-recommended biomarkers ( and ) and an additional six actionable biomarkers. Secondary analyses included tissue versus cfDNA biomarker discovery, overall response rate (ORR), progression-free survival (PFS) to targeted therapy, and positive predictive value (PPV) of cfDNA.
RESULTS
The primary objective was met with cfDNA identifying actionable mutations in 46 patients versus 48 by tissue ( < .05). In total, 0/186 patients were genotyped for all eight biomarkers with tissue, compared with 90.8% using cfDNA. Targetable alterations or were identified in 80.7% when cfDNA was used first versus 57.1% when tissue was used first. PPV for cfDNA-detected was 100.0% (25/25). ORR and PFS in patients receiving targeted therapy based on tissue or cfDNA were similar to those previously reported.
CONCLUSION
This prospective study confirms a previous report that comprehensive cfDNA testing is noninferior to SOC tissue testing in detecting aNSCLC-recommended biomarkers. Furthermore, cfDNA-based first-line therapy produced outcomes similar to tissue-based testing, demonstrating the clinical utility of comprehensive cfDNA genotyping as the initial genotyping modality in patients with treatment-naïve aNSCLC when tissue is insufficient or when all actionable biomarkers cannot be rapidly assessed.
目的
晚期非小细胞肺癌（aNSCLC）的治疗指南建议广泛进行分子谱分析，以选择靶向治疗。本研究前瞻性评估了与标准护理（SOC）组织检测相比，细胞游离循环肿瘤 DNA（cfDNA）的综合下一代测序（NGS），以鉴定 aNSCLC 中指南推荐的改变。
方法
对未经治疗的 aNSCLC 患者进行了经过良好验证的 NGS cfDNA 面板检测，并将结果与 SOC 组织检测进行了比较。主要目的是非劣效性 cfDNA 与组织分析在检测两种指南推荐的生物标志物（和）和另外六种可操作的生物标志物方面。次要分析包括组织与 cfDNA 生物标志物发现、总反应率（ORR）、靶向治疗无进展生存期（PFS）和 cfDNA 的阳性预测值（PPV）。
结果
主要目的是 cfDNA 在 46 名患者中鉴定出 48 名患者的可操作突变（<.05）。总共，186 名患者中有 0 名通过组织进行了所有八种生物标志物的基因分型，而通过 cfDNA 进行了 90.8%。当首先使用 cfDNA 时，可靶向改变或被鉴定为 80.7%，而当首先使用组织时，仅为 57.1%。cfDNA 检测到的 PPV 为 100.0%（25/25）。基于组织或 cfDNA 接受靶向治疗的患者的 ORR 和 PFS 与先前报道的相似。
结论
这项前瞻性研究证实了先前的一项报告，即综合 cfDNA 检测在检测 aNSCLC 推荐的生物标志物方面不劣于 SOC 组织检测。此外，基于 cfDNA 的一线治疗产生的结果与基于组织的检测相似，这表明在组织不足或无法快速评估所有可操作的生物标志物时，综合 cfDNA 基因分型作为治疗初治 aNSCLC 患者的初始基因分型方式具有临床实用性。
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