P1.11-13 Noninvasive Detection of Early Stage NSCLC EGFR Mutations Using Electric Field Induced Release and Measurement (EFIRM)

Abstract

The ability of liquid biopsy to detect circulating tumor mutations has proved especially valuable in the treatment of patients with NSCLC since well characterized variants inform small molecule chemotherapeutic options. EFIRM is a signal amplification technology that allows direct detection of mutations in native plasma and saliva without amplification or sequencing. Previously published work demonstrated a near perfect correlation between biopsy and EFIRM results for the Exon19 del and p.L858R mutations in EGFR in late stage NSCLC patients. In this study we investigated the performance of EFIRM in patients early stage (I and II) NSCLC patients. Plasma samples were collected from 33 healthy controls with biopsy proven benign lung masses and 21 stage I and II NSLC patients with biopsy proven EGFR mutations The samples were immediately centrifuged and frozen. The samples were then blinded and sent for EFIRM analysis. There were 12 biopsies positive for p.L858R (11 stage 1 and 1 stage II) and 9 positive for Exon 19 del (7 stage 1A, and 2 stage II). Using statistically derived cut-offs to optimize sensitivity and specificity, there were 2 false positives (both for p.L858R) in the controls yielding an overall specificity of 91% for the 2 SNP Mutation assay. The sensitivity was 92% for the p.L858R with only one negative in 12 samples in a patient with stage 1 and 77% for Exon 19 del with 2 negatives in 9 samples in a single patient each for stage 1 and 2. The preponderance of patients in this study had stage I NSCLC. The sensitivity of 94% and 77% respectively for the 2 most common mutations is remarkable for patients with Stage 1 lung cancer and a correspondingly low tumor burden and more importantly at a potentially curable stage. We are in the process of improving the technical performance of this assay and adding additional variants to the panel in order to increase clinical utility. These data are promising for the potential use of the EFIRM platform for the purposes of drug selection, disease recurrence, follow-up of indeterminate lung nodules from spiral CT screening programs, and / or population screening.