{"entity":{"id":"aura3","kind":"trial","name":"AURA3","aka":[],"tldr":"Proved that a drug designed against the specific mutation that causes resistance works far better than chemotherapy, and made resistance testing part of routine lung cancer care.","summary":"When a lung cancer driven by an EGFR mutation stops responding to a first- or second-generation inhibitor, about half the time the reason is a second mutation, T790M, in the gatekeeper position of the kinase. Osimertinib was designed to bind that residue covalently while sparing wild-type EGFR. AURA3 randomised 419 patients whose disease had progressed on first-line EGFR inhibition and whose tumour carried T790M 2:1 to osimertinib 80 mg daily or to pemetrexed with carboplatin or cisplatin every three weeks for up to six cycles, with maintenance pemetrexed allowed.\n\nMedian progression-free survival was 10.1 months with osimertinib against 4.4 months with chemotherapy (hazard ratio 0.30, 95 percent confidence interval 0.23 to 0.41), including in patients with central nervous system metastases.\n\nAURA3 confirmed the accelerated approval osimertinib had received in 2015 and established the practice of re-biopsying, or testing plasma for, the resistance mutation at progression. FLAURA then moved osimertinib to first line, which removed most of the T790M population: the mutation arises under pressure from the older drugs, and when they are not used, it is not selected for.","status":"positive","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT02151981","url":"https://clinicaltrials.gov/study/NCT02151981"},{"label":"AURA3 (New England Journal of Medicine 2017)","url":"https://doi.org/10.1056/NEJMoa1612674"},{"label":"NICE TA653: osimertinib for EGFR T790M mutation-positive advanced non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta653"}],"tags":[],"related":[],"cancers":["egfr-mutant-nsclc"],"sections":[],"technologies":["kinase-inhibitors","cytotoxic-chemotherapy","platinum","liquid-biopsy"],"targets":["egfr"],"drugs":["osimertinib","pemetrexed","carboplatin","cisplatin"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["gatekeeper-mutation","resistance","tki-term","brain-metastases"],"trials":["flaura"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02151981","phase":"3","setting":"EGFR T790M-positive advanced non-small-cell lung cancer progressing after a first-line EGFR inhibitor: osimertinib 80 mg daily versus pemetrexed with carboplatin or cisplatin, with investigator-assessed progression-free survival as the primary endpoint","sponsor":"AstraZeneca","result":"Median progression-free survival 10.1 against 4.4 months (hazard ratio 0.30, 95 percent confidence interval 0.23 to 0.41).","yearReported":2017,"enrolled":419,"enrolledBasis":"randomised","enrolledNote":"419 patients were randomised in the primary publication; the ClinicalTrials.gov record for NCT02151981 gives 421.","outcomes":[{"endpoint":"Progression-free survival (investigator assessed)","primary":true,"unit":"months","arms":[{"name":"Osimertinib","value":10.1},{"name":"Platinum and pemetrexed","value":4.4}],"hr":0.3,"ci":[0.23,0.41],"source":"https://doi.org/10.1056/NEJMoa1612674"}],"replication":"Consistent with the single-arm AURA extension and AURA2 cohorts on which the accelerated approval rested."},"route":"/trials/aura3/","neighbours":{"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/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"},{"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":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"},{"id":"pemetrexed","kind":"drug","name":"Pemetrexed","route":"/drugs/pemetrexed/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"term":[{"id":"brain-metastases","kind":"term","name":"Brain metastases (intracranial disease)","route":"/terms/brain-metastases/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"gatekeeper-mutation","kind":"term","name":"On-target resistance mutations (gatekeeper, solvent-front, compound)","route":"/terms/gatekeeper-mutation/"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","route":"/terms/tki-term/"}],"trial":[{"id":"flaura","kind":"trial","name":"FLAURA","route":"/trials/flaura/"}]}}