Tissue and Plasma EGFR Mutation Analysis in the FLAURA Trial: Osimertinib versus Comparator EGFR Tyrosine Kinase Inhibitor as First-Line Treatment in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer.

Abstract

To assess the utility of the <b>cobas</b> EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with <i>EGFR</i>-mutated (<i>EGFR</i>m; Ex19del and/or L858R) advanced or metastatic non-small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125). Tumor tissue <i>EGFR</i>m status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA <i>EGFR</i>m status was retrospectively determined with the central cobas plasma test. Of 994 patients screened, 556 were randomized (289 and 267 with central and local <i>EGFR</i> test results, respectively) and 438 failed screening. Of those randomized from local <i>EGFR</i> test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed <i>EGFR</i>m positive by central cobas tissue test. Using reference central cobas tissue test results, positive percent agreements with cobas plasma test results for Ex19del and L858R detection were 79% [95% confidence interval (CI), 74-84] and 68% (95% CI, 61-75), respectively. Progression-free survival (PFS) superiority with osimertinib over comparator EGFR-TKI remained consistent irrespective of randomization route (central/local <i>EGFR</i>m-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA <i>EGFR</i>m-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months). Our results support utility of cobas tissue and plasma testing to aid selection of patients with <i>EGFR</i>m advanced NSCLC for first-line osimertinib treatment. Lack of <i>EGFR</i>m detection in plasma was associated with prolonged PFS versus patients plasma <i>EGFR</i>m positive, potentially due to patients having lower tumor burden.