Suresh S. RamalingamJohan VansteenkisteDavid PlanchardByoung Chul ChoJhanelle E. GrayYuichiro OheCaicun ZhouThanyanan ReungwetwattanaYing ChengBusyamas ChewaskulyongRiyaz ShahManuel CoboKi Hyeong LeeParneet CheemaMarcello TiseoThomas JohnMeng Chih LinFumio ImamuraTakayasu KurataAlexander ToddRachel HodgeMatilde SaggeseYuri RukazenkovJean Charles SoriaYonsei Cancer CenterJilin Provincial Cancer HospitalShanghai Pulmonary HospitalChang Gung University College of MedicineKU Leuven– University Hospital LeuvenInstitut de Cancerologie Gustave RoussyKansai Medical UniversityUniversité Paris-SudNational Cancer Center HospitalUniversity of TorontoFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityHospital Regional Universitario Carlos HayaUniversità degli Studi di Parma, Facoltà di Medicina e ChirurgiaChungbuk National University, College of MedicineAustin HealthMoffitt Cancer CenterMaidstone HospitalAstraZenecaEmory University School of MedicineChiang Mai UniversityOsaka International Cancer Institute2020-01-272020-01-272020-01-02New England Journal of Medicine. Vol.382, No.1 (2020), 41-5015334406002847932-s2.0-85077224130https://repository.li.mahidol.ac.th/handle/20.500.14594/49643Copyright © 2019 Massachusetts Medical Society. BACKGROUND Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared firstline osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progressionfree survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported. METHODS In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group). Overall survival was a secondary end point. RESULTS The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046). At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively. Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. CONCLUSIONS Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI. The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125.)Mahidol UniversityMedicineArticleSCOPUS10.1056/NEJMoa1913662