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.

Gray, Jhanelle EOkamoto, IsamuSriuranpong, ViroteVansteenkiste, JohanImamura, FumioLee, Jong SeokPang, Yong-KekCobo, ManuelKasahara, KazuoCheng, YingNogami, NaoyukiCho, Eun KyungSu, Wu ChouZhang, GuiliHuang, XiangningLi-Sucholeiki, XiaochengLentrichia, BrianDearden, SimonJenkins, SuzanneSaggese, MatildeRukazenkov, YuriRamalingam, Suresh S2023-01-252023-01-252019-11-15Gray JE, Okamoto I, Sriuranpong V, Vansteenkiste J, Imamura F, Lee JS, et al. 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. Clin Cancer Res. 2019 Nov 15;25(22):6644-6652http://hdl.handle.net/10668/14431To assess the utility of the cobas EGFR Mutation Test, with tissue and plasma, for first-line osimertinib therapy for patients with EGFR-mutated (EGFRm; Ex19del and/or L858R) advanced or metastatic non-small cell lung cancer (NSCLC) from the FLAURA study (NCT02296125). Tumor tissue EGFRm status was determined at screening using the central cobas tissue test or a local tissue test. Baseline circulating tumor (ct)DNA EGFRm status was retrospectively determined with the central cobas plasma test. 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 EGFRm 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 EGFRm-positive tissue test). In both treatment arms, PFS was prolonged in plasma ctDNA EGFRm-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 EGFRm advanced NSCLC for first-line osimertinib treatment. Lack of EGFRm detection in plasma was associated with prolonged PFS versus patients plasma EGFRm positive, potentially due to patients having lower tumor burden.enAcrylamidesAllelesAmino Acid SubstitutionAniline CompoundsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungClinical Decision-MakingAcrylamidesAllelesAmino Acid SubstitutionAniline CompoundsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungClinical Decision-MakingClinical Trials, Phase III as TopicDisease ManagementErbB ReceptorsFemaleHumansLung NeoplasmsMaleMutationNeoplasm MetastasisNeoplasm StagingProtein Kinase InhibitorsRandomized Controlled Trials as TopicTreatment OutcomeTissue 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.research article31439584open accessAcrylamidesAllelesAmino Acid SubstitutionAniline CompoundsAntineoplastic AgentsCarcinoma, Non-Small-Cell Lung10.1158/1078-0432.CCR-19-11261557-3265PMC7209579https://lirias.kuleuven.be/bitstream/123456789/641233/2/1078-0432.CCR-19-1126.full.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209579/pdf