P3.02-002 Liquid and Solid Rebiopsies in EGFR-Mutated NSCLC Patients

Abstract

Treatment of EGFR-mutated NSCLC patients with acquired resistance to EGFR tyrosine kinase inhibitors (TKI) relies on identification of the mechanism of resistance. We performed a retrospective multicentric study in order to investigate use and results of liquid (circulating free DNA) and solid rebiopsies in routine practice. We included 95 EGFR-mutated NSCLC patients with at least one rebiopsy after treatment with EGFR TKI (mostly 1st generation TKI). 87 solid rebiopsies and 71 liquid rebiopsies were performed. The number of liquid biopsies increased over time, from 1/y (6,6% of all rebiopsies in 2014) to 53/y (70,6% of all rebiopsies in 2016). The proportion of liquid biopsies increased with the number of rebiopsies per patient, from 35,5% for the first rebiopsy to 83,3% for the third rebiopsy. The rebiopsy identified a mechanism of acquired resistance in 48 patients (50,5%), including 43 patients with a T790M mutation (45,2%), 2 patients (2,1%) with MET amplification, 1 patient (1%) with small cell lung cancer transformation, 1 patient (1%) with a C797S mutation and 1 patient (1%) with a KRAS mutation. The initial EGFR mutation was found in 74 solid rebiopsies (85%) and 43 liquid rebiopsies (60%). The T790M mutation was found in 32 solid rebiopsies (36,8%) and 18 liquid rebiopsies (25,3%). Among 44 patients having both liquid and solid rebiopsies performed at the same time, an EGFR mutation was found by both techniques in 26 cases (59,1%) and the overall concordance was 88,6%. Analysis of cerebrospinal fluid was positive in 10 patients (100%) for the initial EGFR mutation and 1 patient (10%) for the T790M mutation. A T790M mutation was identified in 37,3% of all first rebiopsies. Repeated rebiopsies when the first biopsy was negative identified the T790M mutation in 29,6% of cases. In our series representative of daily practice, rebiopsies of EGFR-mutated NSCLC patients with acquired resistance to EGFR TKI identified a mechanism of resistance in half of the cases. Repeating rebiopsies increased the chance of detecting a T790M mutation.