P35.05 The Monitoring of Mutated EGFR Levels in Liquid Biopsy from Patients on EGFR-TKIs – Early Detection of NSCLC Progression

Abstract

Non-invasive evaluation of circulating tumor DNA (ctDNA) enables the real-time monitoring of the status and quantitate expression level of mutated EGFR gene (mEGFR) in the blood from NSCLC patients (pts) on EGFR TKIs. We evaluated the feasibility of the longitudinal analysis of mEGFR level in plasma and its effectiveness in early detection of NSCLC progression in pts treated with EGFR TKIs in the first line. Peripheral blood was prospectively collected from 64 advanced, EGFR mutation-positive NSCLC pts at the time of diagnosis (baseline) and then every month during the first line EGFR-TKI treatment (erlotinib, gefitinib, afatinib) until clinical progression. The mutated EGFR ctDNA was analyzed using Cobas EGFR Mutation Test v2 (Roche, Germany). The level of mEGFR in plasma was measured as the Semi-Quantitative Index (SQI). At baseline, 46 out of 64 (72%) pts demonstrated the same activating EGFR mutation in liquid biopsy and tumor tissue (there were no discrepant results). In the remaining 28% pts the mEGFR ctDNA was undetectable in plasma. To date, 33 pts completed the first line EGFR TKI treatment with complete set of plasma samples analyzed for mEGFR ctDNA. The median (min-max) PFS was 10 (2-25) months. In the subgroup of long-term responders to first line EGFR TKIs (PFS≥11 months, n=14, 42%) the complete clearance of baseline mEGFR levels in plasma was observed within 1-2 months of treatment regardless the type of mutation; mEGFR ctDNA remained undetectable during the following months. This phenomenon was not observed in short-term responders (PFS<5.5 months, n=8, 24%). In 17 pts, a rapid raise to or above mEGFR baseline preceded clinical progression by 4-20 weeks, with mean SQI of mEGFR in plasma at baseline 8.59, after first month of treatment 1.69, and 6.73 upon progression. In 8 (24%) pts the T790M resistance mutation was detected upon progression in plasma ctDNA alongside with the primary activating EGFR mutation (mean SQI for T790M was 7.87). In 12 (28%) pts the plasma mEGFR levels were undetectable at diagnosis and throughout the treatment. The dynamic changes of mEGFR ctDNA levels in plasma of NSCLC pts reflect well their response to the first line EGFR TKIs. The longitudinal monitoring of mEGFR levels in plasma allows to observe the disease progression on EGFR TKIs much earlier than conventional imaging techniques. The dynamics of mEGFR ctDNA level in plasma during the first 2 months of treatment may present a predictive value for EGFR TKI therapy. In 28% pts the plasma mEGFR level remains undetectable at diagnosis and during treatment. The study is ongoing.