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

To assess the utility of the EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with -mutated ( m; Ex19del and/or L858R) advanced or metastatic non-small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125). Tumor tissue m status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA 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 test results, respectively) and 438 failed screening. Of those randomized from local test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed 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 m-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA 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 m advanced NSCLC for first-line osimertinib treatment. Lack of m detection in plasma was associated with prolonged PFS versus patients plasma m positive, potentially due to patients having lower tumor burden.