{"entity":{"id":"paper-lu-laura-osimertinib-stage-iii-nejm-2024","kind":"paper","name":"Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC","aka":[],"tldr":"For stage III lung cancer with an EGFR mutation, the standard consolidation immunotherapy works poorly. LAURA gave the EGFR tablet instead and pushed median time to progression from 5.6 months to 39.1.","summary":"The LAURA trial investigators, reported by Lu, Kato, Dong and colleagues with Ramalingam as senior author, randomised 216 patients with unresectable EGFR-mutated stage III non-small-cell lung cancer who had not progressed during or after chemoradiotherapy to osimertinib (143) or placebo (73), in a double-blind, placebo-controlled phase 3 design.\n\nIt closes a hole the PACIFIC regimen left open. Durvalumab consolidation after chemoradiotherapy became standard for stage III disease, but EGFR-mutant tumours respond poorly to checkpoint blockade, so the patients with the most treatable biology in the metastatic setting had the least to gain in the curative one.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2402614"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38828946/"},{"label":"ClinicalTrials.gov NCT03521154","url":"https://clinicaltrials.gov/study/NCT03521154"}],"tags":["lung-evidence"],"related":["paper-pacific-nejm-2017","paper-adaura-nejm-2020","paper-flaura-nejm-2018"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc","stage-iii-unresectable-nsclc"],"sections":["targeted-therapy","radiation"],"technologies":["radiotherapy","imrt-igrt"],"targets":["egfr"],"drugs":["osimertinib","durvalumab"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["chemoradiation","driver-mutation"],"trials":["laura"],"people":["suresh-ramalingam"],"bottlenecks":["b-resistance","b-biomarker-validation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2402614","pmid":"38828946","authors":"Lu S, Kato T, Dong X, et al.","paperType":"rct","findings":["Median progression-free survival by blinded independent central review 39.1 months with osimertinib against 5.6 months with placebo: hazard ratio for progression or death 0.16 (95 percent confidence interval 0.10 to 0.24).","216 patients who had undergone chemoradiotherapy were randomised, 143 to osimertinib and 73 to placebo.","Treatment continued until disease progression or discontinuation of the regimen."],"whatItMeans":"Stage III lung cancer is now treated by genotype as well as by stage: an EGFR mutation moves a patient from durvalumab consolidation to osimertinib consolidation. It is also the strongest hazard ratio in the lung cancer literature, which is a reason to read the overall survival data carefully when they arrive.","caveats":["A hazard ratio of 0.16 on progression-free survival in a setting where the aim is cure; overall survival was immature and the placebo arm could cross over.","Small trial, 216 patients, in a population that has to be found by molecular testing of stage III disease, which is not universal.","Optimal duration of osimertinib, and whether it is deferring recurrence or preventing it, are unanswered."],"changedPractice":true,"participants":216},"route":"/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/","neighbours":{"paper":[{"id":"paper-adaura-nejm-2020","kind":"paper","name":"ADAURA: three years of osimertinib after surgery for EGFR-mutated lung cancer","route":"/key-papers/paper-adaura-nejm-2020/"},{"id":"paper-spigel-pacific-five-year-survival-jco-2022","kind":"paper","name":"Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer","route":"/key-papers/paper-spigel-pacific-five-year-survival-jco-2022/"},{"id":"paper-flaura-nejm-2018","kind":"paper","name":"FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer","route":"/key-papers/paper-flaura-nejm-2018/"},{"id":"paper-pacific-nejm-2017","kind":"paper","name":"PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer","route":"/key-papers/paper-pacific-nejm-2017/"}],"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/"},{"id":"stage-iii-unresectable-nsclc","kind":"cancer","name":"Unresectable stage III non-small-cell lung cancer","route":"/cancers/stage-iii-unresectable-nsclc/"}],"section":[{"id":"radiation","kind":"section","name":"Radiation Therapy","route":"/fronts/radiation/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"term":[{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"radiotherapy","kind":"term","name":"Radiotherapy","route":"/terms/radiotherapy/"}],"technology":[{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"drug":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"}],"trial":[{"id":"laura","kind":"trial","name":"LAURA","route":"/trials/laura/"}],"person":[{"id":"suresh-ramalingam","kind":"person","name":"Suresh S. Ramalingam","route":"/people/suresh-ramalingam/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"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/"}]}}