{"entity":{"id":"paper-flaura-nejm-2018","kind":"paper","name":"FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer","aka":[],"tldr":"Starting with the third-generation EGFR drug osimertinib, rather than saving it for later, kept EGFR-mutated lung cancer under control for almost twice as long and later helped patients live longer.","summary":"Double-blind phase 3 trial of 556 patients with untreated advanced non-small-cell lung cancer carrying an EGFR exon 19 deletion or L858R mutation, randomised to osimertinib or a first-generation EGFR inhibitor (gefitinib or erlotinib). Primary endpoint was investigator-assessed PFS.\n\nMedian PFS was 18.9 vs 10.2 months (HR 0.46), with fewer central nervous system progressions and less grade 3 toxicity. The 2020 overall survival report showed 38.6 vs 31.8 months (HR 0.80) despite crossover. It made osimertinib the global first-line standard and the backbone on which FLAURA2 and MARIPOSA later built.","asOf":"2026-09-08","links":[{"label":"NEJM 2018","url":"https://doi.org/10.1056/NEJMoa1713137"},{"label":"NEJM 2020 (OS)","url":"https://doi.org/10.1056/NEJMoa1913662"},{"label":"ClinicalTrials.gov NCT02296125","url":"https://clinicaltrials.gov/study/NCT02296125"}],"tags":[],"related":["lung-cancer-evidence-roadmap","paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023","paper-mariposa-nejm-2024"],"cancers":["nsclc","lung-cancer"],"sections":[],"technologies":["kinase-inhibitors","cgp"],"targets":["egfr"],"drugs":["osimertinib"],"companies":["astrazeneca"],"institutions":["gustave-roussy"],"pathways":[],"terms":["oncogene-addiction","resistance","pfs","os","first-line"],"trials":["flaura2","mariposa","adaura"],"people":["jean-charles-soria","ohe-yuichiro","zhou-caicun","cho-byoung-chul"],"bottlenecks":["b-resistance","b-brain-delivery","b-global-access"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/NEJMoa1713137","authors":"Soria JC, Ohe Y, Vansteenkiste J, et al.","paperType":"rct","findings":["Median PFS 18.9 vs 10.2 months; HR 0.46 (95% CI 0.37-0.57).","CNS progression events were roughly halved with osimertinib.","Grade 3 or higher adverse events 34% vs 45%.","Overall survival (2020): median 38.6 vs 31.8 months, HR 0.80 (95% CI 0.64-1.00), with about 31% of control patients crossing over to osimertinib.","FLAURA2 (2023) later showed adding platinum-pemetrexed to osimertinib extends PFS further (25.5 vs 16.7 months, HR 0.62)."],"whatItMeans":"Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.","caveats":["The overall survival benefit was borderline (upper confidence limit 1.00) and diluted by crossover to osimertinib.","Asian patients and those with L858R had smaller OS gains in subgroup analyses.","Resistance is universal; the trial did not address what to do after osimertinib.","High drug cost limits access in many countries where EGFR mutations are common."],"changedPractice":true,"participants":556},"route":"/key-papers/paper-flaura-nejm-2018/","neighbours":{"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}],"paper":[{"id":"paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","kind":"paper","name":"Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma","route":"/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/"},{"id":"paper-mariposa-nejm-2024","kind":"paper","name":"MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer","route":"/key-papers/paper-mariposa-nejm-2024/"},{"id":"paper-lu-laura-osimertinib-stage-iii-nejm-2024","kind":"paper","name":"Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC","route":"/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/"},{"id":"paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023","kind":"paper","name":"Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC","route":"/key-papers/paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023/"}],"cancer":[{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"drug":[{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"institution":[{"id":"gustave-roussy","kind":"institution","name":"Gustave Roussy","route":"/institutions/gustave-roussy/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"first-line","kind":"term","name":"Lines of therapy","route":"/terms/first-line/"},{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"adaura","kind":"trial","name":"ADAURA","route":"/trials/adaura/"},{"id":"flaura","kind":"trial","name":"FLAURA","route":"/trials/flaura/"},{"id":"flaura2","kind":"trial","name":"FLAURA2","route":"/trials/flaura2/"},{"id":"mariposa","kind":"trial","name":"MARIPOSA","route":"/trials/mariposa/"}],"person":[{"id":"cho-byoung-chul","kind":"person","name":"Byoung Chul Cho","route":"/people/cho-byoung-chul/"},{"id":"zhou-caicun","kind":"person","name":"Caicun Zhou","route":"/people/zhou-caicun/"},{"id":"jean-charles-soria","kind":"person","name":"Jean-Charles Soria","route":"/people/jean-charles-soria/"},{"id":"ohe-yuichiro","kind":"person","name":"Yuichiro Ohe","route":"/people/ohe-yuichiro/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"},{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-bio1-molecular-progression-add-on","kind":"idea","name":"Add a drug when the blood test turns, without stopping the one that works","route":"/ideas/idea-bio1-molecular-progression-add-on/"},{"id":"idea-bio1-upfront-bypass-combination","kind":"idea","name":"Add the second drug on day one when the escape route is predictable","route":"/ideas/idea-bio1-upfront-bypass-combination/"},{"id":"idea-moon-closed-loop-adaptive-therapy","kind":"idea","name":"Autonomous closed-loop adaptive therapy driven by blood tests and evolutionary models","route":"/ideas/idea-moon-closed-loop-adaptive-therapy/"},{"id":"idea-bio1-ctdna-adaptive-tki","kind":"idea","name":"ctDNA-guided dose holidays for lung cancer targeted therapy","route":"/ideas/idea-bio1-ctdna-adaptive-tki/"},{"id":"idea-ferroptosis-persisters","kind":"idea","name":"Kill drug-tolerant persisters through ferroptosis","route":"/ideas/idea-ferroptosis-persisters/"},{"id":"idea-bio1-baseline-ultradeep-resistant-clones","kind":"idea","name":"Look for the resistant sub-population before the first dose","route":"/ideas/idea-bio1-baseline-ultradeep-resistant-clones/"},{"id":"idea-bio2-brain-met-prevention-trials","kind":"idea","name":"Prevention trials aimed only at brain metastasis","route":"/ideas/idea-bio2-brain-met-prevention-trials/"},{"id":"idea-bio1-apobec-inhibitor-adjunct","kind":"idea","name":"Slow the tumour's mutation engine with APOBEC inhibitors during targeted therapy","route":"/ideas/idea-bio1-apobec-inhibitor-adjunct/"},{"id":"idea-tr2-alternating-vs-concurrent","kind":"idea","name":"Test alternating drug schedules against giving both drugs at once","route":"/ideas/idea-tr2-alternating-vs-concurrent/"},{"id":"idea-fund-brain-metastases-programme","kind":"idea","name":"Treat brain metastases as a disease with its own trials programme","route":"/ideas/idea-fund-brain-metastases-programme/"}]}}