Abstract 4460: Clinical utility of comprehensive cell-free DNA (cfDNA) analysis to identify genomic biomarkers in newly diagnosed metastatic non-small cell lung cancer (mNSCLC)
Authors: Leighl Natasha , Page Ray D. , Raymond Victoria M. , Daniel Davey , Divers Stephen , Reckamp Karen L. , Villalona-Calero Miguel A. , Dix Daniel , Jackson Matthew , Odegaard Justin I. , Papadimitrakopoulou Vassiliki A. 
Published: August 2019

Abstract
Background: The number of guideline-recommended biomarkers to be assessed in patients (pts) with newly-diagnosed mNSCLC is increasing and includes both predictive (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2; “Guideline-7”(G7)) and prognostic (KRAS) targets. cfDNA analysis is a viable alternative to tissue genotyping, especially in tissue- or time-limited clinical scenarios. We aimed to demonstrate the non-inferiority of comprehensive cfDNA, relative to standard of care (SOC) tissue genotyping, to identify guideline-recommended genomic biomarkers in pts with mNSCLC.
Methods: Pts with previously untreated non-squamous mNSCLC undergoing SOC tissue genotyping were prospectively enrolled at 28 North American centers between July 2016 - April 2018. Pts submitted a pre-treatment blood sample for cfDNA analysis utilizing a CLIA-certified comprehensive 73-gene next generation sequencing panel (Guardant360®). Turn-around time (TAT) was defined as time from test order to final results.
Results: 282 pts with pre-treatment cfDNA samples were included. Most pts were white (81.9%) and half were female (54.3%). A G7 biomarker was identified in tissue in 60 pts and by cfDNA in 77 pts (21.3% versus 27.3%; p&lt;0.0001). In the 60 tissue-positive pts, the biomarker was identified in tissue alone (12) or concordant with plasma (48). Utilizing cfDNA increased the number of patients with an identified G7 biomarker by 48%, from 60 pts to 89, including those with negative (7), not assessed (16), or quantity not sufficient (QNS)(6) results in tissue. Of 193 pts without a G7 biomarker by tissue or cfDNA, 24 (12.4%) had an activating KRAS alteration identified in tissue alone (3) or concordant with cfDNA (21). cfDNA increased the number of KRAS-positive pts from 24 to 92 (tissue negative=3; not assessed=60; QNS=5). Positive predictive value (PPV) for cfDNA vs. tissue genotyping for FDA approved targets (EGFR, ALK, ROS1, BRAF) was 100%. Median TAT was significantly lower for cfDNA as compared to tissue genotyping (9 vs 15 days; p&lt;0.0001).
Discussion: In the largest cfDNA study in previously untreated mNSCLC, we demonstrate that cfDNA detects G7 biomarkers at a rate similar to tissue, meeting the primary study objective. Additionally, even in this population where tissue genotyping was required, cfDNA rescued 30.2% (85/282) of pts including those who were tissue QNS and those who were incompletely genotyped or negative for the biomarker in tissue. The findings in this prospective, multicenter North American study confirm similar findings in Europe and add to the growing evidence that cfDNA can be successfully used to completely assess and identify G7 biomarkers significantly faster than tissue testing, can rescue G7-positive patients with non-diagnostic tissue results, and demonstrates the clinical utility of cfDNA in newly diagnosed mNSCLC.
Citation Format: Natasha Leighl, Ray D. Page, Victoria M. Raymond, Davey Daniel, Stephen Divers, Karen L. Reckamp, Miguel A. Villalona-Calero, Daniel Dix, Matthew Jackson, Justin I. Odegaard, Vassiliki A. Papadimitrakopoulou. Clinical utility of comprehensive cell-free DNA (cfDNA) analysis to identify genomic biomarkers in newly diagnosed metastatic non-small cell lung cancer (mNSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4460.