Abstract A26: Defining VALUE: Routine liquid biopsy in NSCLC diagnosis—a Canadian trial in progress
Authors: Agulnik Jason , Law Jennifer H. , Juergens Rosalyn , Laskin Janessa , Laurie Scott , Hao Desiree , Ezeife Doreen A. , Le Lisa W. , Kiedrowski Lesli A. , Lanman Richard B. , Leighl Natasha B. 
Published: June 2020

Abstract
Background: Genotyping tumor tissue in time for clinical treatment decision-making has been challenging in advanced non-small cell lung cancer (NSCLC). Next-generation sequencing (NGS) of cell-free DNA (cfDNA) obtained from blood samples may improve diagnostic testing, with faster turnaround time (TAT) and potential cost savings. This study defines the added value of cfDNA versus tumor tissue genotyping in patients with advanced NSCLC in the Canadian public health care system.
Methods: Patients with advanced non-squamous NSCLC patients at 6 cancer centers across Canada are being recruited (BC, Alberta, Ontario, Quebec). Two cohorts are included: 1) treatment-naïve patients with ≤10 pack year smoking history (N=150) and 2) patients with known oncogenic drivers (e.g., EGFR, ALK, ROS1, BRAF) that have progressed on tyrosine kinase inhibitors (N=60). Consenting patients undergo peripheral blood draw and cfDNA NGS analysis using Guardant360™ (Guardant Health), a validated assay that detects alterations in 74 known cancer-associated genes, prior to starting treatment (Cohort 1) or next line of treatment (Cohort 2). Standard-of-care (SOC) tissue profiling is completed per institutional standards. Endpoints include response, progression-free survival, time-to-treatment failure, as well as time to treatment initiation, number of actionable genomic alterations identified, result TAT, patient-reported quality of life (EQ-5D), and willingness to pay. A decision-analytic model will be developed to perform a cost-consequence analysis of cfDNA versus tissue-based diagnostics.
Results: Between February and October 3, 2019, 49 patients (32 female, 17 male) were recruited to Cohort 1 and 31 (21 female, 10 male) to Cohort 2. Forty patients in Cohort 1 (81.6%) had ≥1 alteration detected, with a total of 145 genetic alterations detected in 36 genes. Of these, 68 were actionable with FDA-approved drugs and/or clinical trials available. The most frequent actionable alterations were in EGFR (33.8%), MET Exon 14 Skipping (7.4%), and EML4-ALK fusion (2.9%). Additional alterations included TP53 (29.4%), KRAS (8.8%), PIK3CA (4.4%), and STK11 (2.9%). In Cohort 2, 29 patients (93.5%, 29/31) had ≥1 alteration detected, with a total of 130 alterations in 33 genes. The most frequent alterations were in EGFR (46.0%), TP53 (9.5%), EML4-ALK fusion (6.3%), ALK mutations (4.8%), and BRAF, BRCA2, GNAS, KRAS, MET Exon 14 Skipping, NRAS, and PTEN (each 3.2%). In samples with alterations detected, the median number of alterations/patient was 3 (range 1-17). The median time to Guardant report was 8 days (range 5-27). Mutations detected in tissue, concordance, and time to result for SOC tissue profiling will be updated, along with incremental treatment options for patients.
Conclusion: Over 86% of advanced NSCLC patients had detectable cfDNA and at least 61 had actionable mutations. Blood-based testing may be an important cost-efficient addition to tissue-based testing in lung cancer to determine optimal treatment options.
Citation Format: Jason Agulnik, Jennifer H. Law, Rosalyn Juergens, Janessa Laskin, Scott Laurie, Desiree Hao, Doreen A. Ezeife, Lisa W. Le, Lesli A. Kiedrowski, Richard B. Lanman, Natasha B. Leighl. Defining VALUE: Routine liquid biopsy in NSCLC diagnosis—a Canadian trial in progress [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A26.