1. 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.
- Author
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Gray JE, Okamoto I, Sriuranpong V, Vansteenkiste J, Imamura F, Lee JS, Pang YK, Cobo M, Kasahara K, Cheng Y, Nogami N, Cho EK, Su WC, Zhang G, Huang X, Li-Sucholeiki X, Lentrichia B, Dearden S, Jenkins S, Saggese M, Rukazenkov Y, and Ramalingam SS
- Subjects
- Acrylamides administration & dosage, Acrylamides adverse effects, Alleles, Amino Acid Substitution, Aniline Compounds administration & dosage, Aniline Compounds adverse effects, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung metabolism, Clinical Decision-Making, Clinical Trials, Phase III as Topic, Disease Management, ErbB Receptors genetics, ErbB Receptors metabolism, Female, Humans, Lung Neoplasms diagnosis, Lung Neoplasms metabolism, Male, Neoplasm Metastasis, Neoplasm Staging, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Randomized Controlled Trials as Topic, Treatment Outcome, Acrylamides therapeutic use, Aniline Compounds therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Mutation, Protein Kinase Inhibitors therapeutic use
- Abstract
Purpose: To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR -mutated ( EGFR m; Ex19del and/or L858R) advanced or metastatic non-small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125)., Experimental Design: Tumor tissue EGFR m status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFR m status was retrospectively determined with the central cobas plasma test., Results: Of 994 patients screened, 556 were randomized (289 and 267 with central and local EGFR test results, respectively) and 438 failed screening. Of those randomized from local EGFR test results, 217 patients had available central test results; 211/217 (97%) were retrospectively confirmed EGFR 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 EGFR m-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFR m-negative (23.5 and 15.0 months) versus -positive patients (15.2 and 9.7 months)., Conclusions: Our results support utility of cobas tissue and plasma testing to aid selection of patients with EGFR m advanced NSCLC for first-line osimertinib treatment. Lack of EGFR m detection in plasma was associated with prolonged PFS versus patients plasma EGFR m positive, potentially due to patients having lower tumor burden., (©2019 American Association for Cancer Research.)
- Published
- 2019
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