Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non–small Cell Lung Cancer
| Autor: | Davey B. Daniel, Stephen G. Divers, Miguel A. Villalona-Calero, Daniel Dix, Richard B. Lanman, Natasha B. Leighl, Ray D. Page, Vassiliki A. Papadimitrakopoulou, Victoria M. Raymond, Justin I. Odegaard, Karen L. Reckamp |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty business.industry Concordance Newly diagnosed medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Cell-free fetal DNA 030220 oncology & carcinogenesis Internal medicine medicine Biomarker (medicine) In patient Non small cell Lung cancer business Genotyping |
| Zdroj: | Clinical Cancer Research. 25:4691-4700 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | 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.See related commentary by Meador and Oxnard, p. 4583 |
| Databáze: | OpenAIRE |
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