P3.02b-032 Association between EGFR T790M Mutation Copy Numbers in Cell-Free Plasma DNA and Response to Osimertinib in Advanced NSCLC: Topic: EGFR Biomarkers

Abstract

Patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC) who developed the T790M resistance mutation during treatment with EGFR tyrosine kinase inhibitors (TKIs) benefit from treatment with third-generation EGFR TKIs such as osimertinib. Treatment with osimertinib requires the confirmation of the presence of the T790M mutation by re-biopsy of the tumor or by analysis of cell-free plasma DNA from blood samples (liquid biopsy). The purpose of our study was to compare T790M mutation copy numbers in cell-free plasma DNA with response to osimertinib. From April 2015 to June 2016, we included 44 patients with advanced T790M-positive NSCLC who received osimertinib after previous disease progression with an EFGR TKI and in whom response to osimertinib was evaluable. T790M mutation status was assessed by droplet digital PCR in cell-free plasma DNA. The threshold for T790M positivity was >1 copy/mL. The T790M mutation status was assessed in all patients by liquid biopsy and in 18 patients also by re-biopsy of the tumor. All 44 patients were T790M-positive in the liquid biopsy. Two out of 18 (11%) patients had a T790M-negative re-biopsy. Thirty-seven patients (86%) showed a response to treatment with osimertinib: 13 (29.5%) complete responses (CR), 24 (54.5%) partial responses (PR), one (2%) stable disease (SD), and six (14%) progressive disease (PD) (Table 1). We observed no statistically significant association between response to osimertinib and T790M copy numbers (p=0.54; Table 1). The median T790M copy numbers across response categories were: CR 25 copies/mL (range 1.7-38092 copies/mL), PR 14 copies/mL (range 1.6-7282 copies/mL), SD+PD 6 copies/mL (range 1.8-475 copies/mL).Table 1ResponseCopies/mLCRPRSDPD<105 (39%)11 (46%)0 (0%)4 (67%)≥108 (62%)13 (54%)1 (100%)2 (33%) Open table in a new tab Patients benefited from osimertinib treatment independent of T790M copy numbers in the blood samples. Although limited by low numbers, we observed a trend towards better response to osimertinib in patients with ≥10 T790M copies/mL.