Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non-small Cell Lung Cancer

被引:448
作者
Leighl, Natasha B. [1 ]
Page, Ray D. [2 ]
Raymond, Victoria M. [3 ]
Daniel, Davey B. [4 ]
Divers, Stephen G. [5 ]
Reckamp, Karen L. [6 ]
Villalona-Calero, Miguel A. [7 ]
Dix, Daniel [3 ]
Odegaard, Justin I. [3 ]
Lanman, Richard B. [3 ]
Papadimitrakopoulou, Vassiliki A. [8 ]
机构
[1] Princess Margaret Canc Ctr, Toronto, ON, Canada
[2] Ctr Canc & Blood Disorders, Ft Worth, TX USA
[3] Guardant Hlth In, Redwood City, CA USA
[4] Tennessee Oncol, Chattanooga, TN USA
[5] Genesis Canc Ctr, Hot Springs, AR USA
[6] City Hope Comprehens Canc Ctr, Duarte, CA USA
[7] Miami Canc Inst, Miami, FL USA
[8] MD Anderson Comprehens Canc Ctr, Houston, TX USA
关键词
CRIZOTINIB; GUIDELINE; BIOPSIES;
D O I
10.1158/1078-0432.CCR-19-0624
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: 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. Patients and Methods: Prospectively enrolled patients with previously untreated mNSCLC undergoing physician discretion SOC tissue genotyping submitted a pretreatment blood sample for comprehensive cfDNA analysis (Guardant360). Results: 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%; P < 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 guidelinerecommended biomarker. For FDA-approved targets (EGFR, ALK, ROS1, BRAF) concordance was > 98.2% with 100% positive predictive value for cfDNA versus tissue (34/34 EGFR-, ALK-, or BRAF-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; P < 0.0001). Guideline-complete genotyping was significantly more likely (268 vs. 51; P < 0.0001). Conclusions: 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 asSOCtissue genotyping, with high tissue concordance, more rapidly and completely than tissue-based genotyping.
引用
收藏
页码:4691 / 4700
页数:10
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