Detection of EGFR-Activating and T790M Mutations by Liquid Biopsy in Patients with EGFR-Mutated Non-Small-Cell Lung Cancer Who Have Progressed to First- and Second-Generation Tyrosine Kinase Inhibitors: A Multicenter Real-Life Retrospective Study

Abstract Objectives In advanced EGFR-mutated NSCLC patients who have progressed to first- and second-generation tyrosine kinase inhibitors (TKIs), liquid biopsy (LB) is routinely used to evaluate the presence of EGFR T790M as an acquired resistance mechanism. The objective of this study was to assess a real-life picture of EGFR T790M detection in LB. Materials and Methods LBs performed between June 2016 and October 2018 for advanced EGFR-mutated NSCLC at progression to first- and second-generation TKIs were retrospectively evaluated in 5 Italian centers. ctDNA was extracted from plasma and tested with different commercial kits. The detection rate in LBs and the patients’ characteristics were correlated. Results 120 patients were consecutively enrolled. The overall T790M detection rate observed by LB was 25.8%. Fifty-four of 89 (60.7%) patients with negative LB results underwent tissue re-biopsy, and 56% were found to be positive for T790M. The overall rate of T790M positivity in the study cohort was 49.2%. LB performed before formal tumor progression according to the RECIST criteria was negative for T790M in all patients (n = 21; P = 0.012). T790M positivity was statistically significantly higher in cases of progression at extra-thoracic metastatic sites (P = 0.008) and, specifically, in the case of worsening bone disease (P = 0.003). Conclusion Our study shows that the detection of T790M-positive patients progressed to first- and second-generation TKIs in real-life was according to the literature. However, this result was obtained with a specific clinical course (repeat LBs and tissue re-biopsy), thus implying the necessity for multidisciplinary management.