Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Center for Cancer and Blood Disorders, Fort Worth, Texas.
Clin Cancer Res. 2019 Aug 1;25(15):4691-4700. doi: 10.1158/1078-0432.CCR-19-0624. Epub 2019 Apr 15.
Complete and timely tissue genotyping is challenging, leading to significant numbers of patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) being undergenotyped for all eight genomic biomarkers recommended by professional guidelines. We aimed to demonstrate noninferiority of comprehensive cell-free DNA (cfDNA) relative to physician discretion standard-of-care (SOC) tissue genotyping to identify guideline-recommended biomarkers in patients with mNSCLC.
Prospectively enrolled patients with previously untreated mNSCLC undergoing physician discretion SOC tissue genotyping submitted a pretreatment blood sample for comprehensive cfDNA analysis (Guardant360).
Among 282 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 60 patients versus 77 cfDNA identified patients (21.3% vs. 27.3%; < 0.0001 for noninferiority). In tissue-positive patients, the biomarker was identified alone (12/60) or concordant with cfDNA (48/60), an 80% cfDNA clinical sensitivity for any guideline-recommended biomarker. For FDA-approved targets () concordance was >98.2% with 100% positive predictive value for cfDNA versus tissue (34/34 or -positive patients). Utilizing cfDNA, in addition to tissue, increased detection by 48%, from 60 to 89 patients, including those with negative, not assessed, or insufficient tissue results. cfDNA median turnaround time was significantly faster than tissue (9 vs. 15 days; < 0.0001). Guideline-complete genotyping was significantly more likely (268 vs. 51; < 0.0001).
In the largest cfDNA study in previously untreated mNSCLC, a validated comprehensive cfDNA test identifies guideline-recommended biomarkers at a rate at least as high as SOC tissue genotyping, with high tissue concordance, more rapidly and completely than tissue-based genotyping..
全面且及时的组织基因分型具有挑战性，导致大量新诊断的转移性非小细胞肺癌（mNSCLC）患者未能对所有八项专业指南推荐的基因组生物标志物进行基因分型。我们旨在证明与医生判断标准护理（SOC）组织基因分型相比，全面的游离 DNA（cfDNA）在识别 mNSCLC 患者指南推荐的生物标志物方面具有非劣效性。
前瞻性纳入接受医生判断 SOC 组织基因分型的未经治疗的 mNSCLC 患者，提交一份预处理血液样本进行全面的 cfDNA 分析（Guardant360）。
在 282 名患者中，医生判断 SOC 组织基因分型在 60 名患者中确定了指南推荐的生物标志物，而 cfDNA 确定了 77 名患者（21.3%比 27.3%；<0.0001 为非劣效性）。在组织阳性患者中，该生物标志物单独确定（12/60）或与 cfDNA 一致（48/60），cfDNA 对任何指南推荐的生物标志物的临床敏感性为 80%。对于 FDA 批准的靶点（），cfDNA 与组织的一致性>98.2%，阳性预测值为 100%（34/34 或 -阳性患者）。与组织相比，额外使用 cfDNA 可将检测率提高 48%，从 60 例增加到 89 例，包括阴性、未评估或组织结果不足的患者。cfDNA 的中位周转时间明显快于组织（9 天比 15 天；<0.0001）。指南完整的基因分型明显更有可能（268 比 51；<0.0001）。
在之前未经治疗的 mNSCLC 的最大 cfDNA 研究中，经过验证的全面 cfDNA 测试确定指南推荐的生物标志物的速度至少与 SOC 组织基因分型一样高，与组织具有高度一致性，并且比基于组织的基因分型更快、更完整。
