121PLungBEAM: A prospective multicenter trial to monitor EGFR mutations using BEAMing technology in stage IV NSCLC patients

Background: Liquid biopsy is a promising approach to improve the management of NSCLC patients, as it offers a minimally-invasive alternative to tumor tissue testing and enables timely monitoring of patients on-therapy. The goal of the present study was to evaluate the clinical value of longitudinal testing of EGFR mutation status in plasma of tissue EGFR mutation-positive NSCLC patients during first-line EGFR TKI therapy across 19 Spanish hospitals to: 1) determine the timing of T790M mutation emergence and 2) monitor EGFR mutation levels in plasma during first-line EGFR TKI therapy with respect to radiological progression. Methods: Blood samples from 109 therapy-naïve advanced NSCLC patients were collected at baseline and monthly throughout EGFR TKI standard therapy. Results from OncoBEAM EGFR mutation were performed by Sysmex in Hamburg, and compared to those obtained by the EGFR tissue testing obtained at the referring hospital. The times at which T790M were first detected in blood were compared to the date of progression as determined by radiological imaging in standard clinical practice. Results: At baseline, the initial positive percent agreement (PPA) for EGFR mutation status in 78 out of 109 patients enrolled in this study was 71.6%. From a total of 60 patients out of 89 who completed the study showing either clinical or radiological progression, 20 patients (33.3%) showed presence of the T790M mutation in plasma during follow-up. In 13 of these patients plasma T790M-positivity was detected an average of 14 weeks prior to radiological progression. Furthermore, the clearance of EGFR mutations in plasma at 8 weeks after initiation of EGFR TKI was a favorable indicator for PFS (37.3 weeks with clearance vs 25.5 weeks in patients without clearance). Patients showing EGFR mutation clearance at 8 weeks had an average baseline MAF of 3.6%, whereas patients with detectable mutations at 8 weeks showed an average baseline value of 13% MAF. Conclusions: Overall, these results show high PPA of plasma and tissue EGFR mutation status at baseline. Early EGFR mutation clearance may be predictive of response to first-line EGFR TKI therapy. Plasma detection of T790M mutation anticipates clinical progression. Clinical trial identification: SYS-ONC-2015-01. Legal entity responsible for the study: Sysmex Inostics GmbH. Funding: Sysmex Inostics GmbH. Disclosure: All authors have declared no conflicts of interest.