Format

Send to

Choose Destination
Clin Cancer Res. 2019 Apr 15. doi: 10.1158/1078-0432.CCR-19-0624. [Epub ahead of print]

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

Author information

1
Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Natasha.Leighl@uhn.ca.
2
Center for Cancer and Blood Disorders, Fort Worth, Texas.
3
Guardant Health, In, Redwood City, California.
4
Tennessee Oncology, Chattanooga, Tennessee.
5
Genesis Cancer Center, Hot Springs, Arkansas.
6
City of Hope Comprehensive Cancer Center, Duarte, California.
7
Miami Cancer Institute, Miami, Florida.
8
MD Anderson Comprehensive Cancer Center, Houston, Texas.
#
Contributed equally

Abstract

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 guideline-recommended 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 as SOC tissue genotyping, with high tissue concordance, more rapidly and completely than tissue-based genotyping.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center