RT Journal Article
T1 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.
A1 Gray, Jhanelle E
A1 Okamoto, Isamu
A1 Sriuranpong, Virote
A1 Vansteenkiste, Johan
A1 Imamura, Fumio
A1 Lee, Jong Seok
A1 Pang, Yong-Kek
A1 Cobo, Manuel
A1 Kasahara, Kazuo
A1 Cheng, Ying
A1 Nogami, Naoyuki
A1 Cho, Eun Kyung
A1 Su, Wu Chou
A1 Zhang, Guili
A1 Huang, Xiangning
A1 Li-Sucholeiki, Xiaocheng
A1 Lentrichia, Brian
A1 Dearden, Simon
A1 Jenkins, Suzanne
A1 Saggese, Matilde
A1 Rukazenkov, Yuri
A1 Ramalingam, Suresh S
K1 Acrylamides
K1 Alleles
K1 Amino Acid Substitution
K1 Aniline Compounds
K1 Antineoplastic Agents
K1 Carcinoma, Non-Small-Cell Lung
K1 Clinical Decision-Making
AB To 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.
PB American Association for Cancer Research
YR 2019
FD 2019-11-15
LK http://hdl.handle.net/10668/14431
UL http://hdl.handle.net/10668/14431
LA en
NO Gray 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):6644-6652
NO The authors thank all the patients and their families. The study (NCT02296125) was funded by AstraZeneca, Cambridge, United Kingdom, the manufacturer of osimertinib. The authors would like to acknowledge Helen Brown, Alex Kohlmann, and Milena Kohlmann for supporting diagnostic data collection and interpretation, andRachel Hodge and Alexander Todd for providing statistical support. The authors acknowledge Roche MolecularSystems Inc. (Pleasanton, CA), the manufacturer of the cobas EGFR Mutation Test v1 and v2. The authors alsoacknowledge Natalie Griffiths, PhD, of iMed Comms, Macclesfield, United Kingdom, an Ashfield Company, part of UDG Healthcare plc for medical writing support that was funded by AstraZeneca, Cambridge, United Kingdom, in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
DS RISalud
RD Apr 10, 2025