Abstract 3912
Background
15–40% of NSCLC patients harbor EGFR sensitizing mutations. Tyrosine kinase inhibitors (TKI) provide significant clinical benefit in this population, yet all patients will develop resistance. Liquid biopsy has been demonstrated to reliably identify somatic tumor associated EGFR mutations. Quantitative assessment of mutated EGFR driven tumors could potentially be used to monitor disease progression and assess therapeutic response.
Methods
129 patients (68 F/61 M) with tissue biopsy-proofed EGFR sensitizing mutation-positive lung adenocarcinoma who were treated with EGFR-TKI and had one before TKI treatment and at least three post TKI treatment/follow-up blood samples were included in the study. 71% (92/129) patients were non-smokers. Plasma samples were tested with the cobas® EGFR Mutation Test v2, and the Semi-Quantitative Index (SQI) values for each mutation were reported by the software for the target mutation. The SQI is able to reflect a trend in the plasma EGFR mutation load. Molecular progression (MP) is defined as two consecutive non-zero SQI values or detection of T790M.
Results
The most common EGFR mutations detected in the tissue were L858R (53%) and Exon 19 deletion (Ex19Del) (40%). One patient had both Ex19Del and T790M mutations. Plasma cfDNA analyses detected EGFR mutations in 74% (95/129) of the baseline samples. 64 of the 95 patients had MP. On average, MP was 42 days prior to clinical progression (CP) based on RECIST1.1. The PPV and NPV of using MP to predict CP were 84% and 68%, respectively. Analysis of the serial plasmas collected from patients who progressed while on 1st line TKI showed reappearance of the original EGFR sensitizing mutations with increasing SQI levels before emergence of a T790M mutation. T790M mutation was detected in 21% (27/129) of the patients on TKI treatment.
Conclusions
This study clearly demonstrated that monitoring EGFR mutation levels or changes in blood could be a meaningful approach to predict clinical progression for lung adenocarcinoma patients treated with EGFR-TKI. It warrants further studies to demonstrate the potential clinical utility of serial blood EGFR testing in NSCLC management.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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