P3.02b-095 Tracing Spatiotemporal T790M Heterogeneity in Patients with EGFR-Mutant Advanced NSCLC after Acquired Resistance to EGFR TKIs: Topic: EGFR RES

Abstract

With the marketing of osimertinib, epidermal growth factor receptor (EGFR) T790M mutation has become a clinically significant biomarker for advanced EGFR-mutant non-small-cell lung cancer (NSCLC) after acquired resistance to previous EGFR TKIs. However, T790M status might vary spatiotemporally and consequently hinder the initiation and clinical efficacy of third generation EGFR TKIs. Till now, the spatiotemporal traces of T790M under treatment pressure have not been fully elucidated. We retrospectively reviewed T790M status and clinical courses of 93 patients who underwent multiple (≥2) rebiopsies after acquired resistance to first or second generation EGFR TKIs from 2010 to 2015 in Guangdong General Hospital. Patients underwent synchronous rebiopsies at the same lesion or paired tissue and plasma rebiopsies were enrolled to evaluate the spatial T790M heterogeneity. Patients received heterochronous rebiopsies at the same lesion or different lesions were enrolled to evaluate the temporal and spatiotemporal T790M heterogeneity respectively.Tissue EGFR detection was performed by SNAPSHOT or Amplification Refractory Mutation System (ARMS). Plasma EGFR was detected by ARMS. A total of 99 evaluations were performed with 6 of 93 enrolled patients underwent both synchronous and heterochronous rebiopsies. Among 20 patients who underwent synchronous rebiopsies at the same lesion, 13 revealed T790M heterogeneity. Among 17 patients who had paired tissue and plasma rebiopsies, 8 showed T790M heterogeneity. Spatial T790M heterogeneity ratio was 57% (21/37) in general. 33% (10/30) patients who received heterochronous rebiopsies at the same lesion revealed temporal T790M heterogeneity. Spatiotemporal T790M heterogeneity was observed in 53% (17/32) of patients who received heterochronous multiple sites rebiopsies. Of abovementioned patients with heterochronous T790M heterogeneity, T790M status in 67% (18/27) switched from negative to positive after chemotherapy or continuation of EGFR TKIs and in 33% (9/27) switched from positive to negative after chemotherapy or combined regimens of chemotherapy and EGFR TKIs. T790M status could vary spatiotemporally at a ratio of 33-57% in patients with acquired resistance to previous EGFR TKIs. Repeated rebiopsies both at the same lesion and various lesions might be valued particularly in T790M-negative cases in this subset of patients.