{"entity":{"id":"paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023","kind":"paper","name":"Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC","aka":[],"tldr":"FLAURA2 added chemotherapy to the standard EGFR tablet in 557 patients and cut the risk of the cancer growing by 38 percent, at the cost of chemotherapy's side effects for everybody.","summary":"The FLAURA2 investigators, reported by Planchard, Jänne, Cheng and colleagues, randomised 557 patients with previously untreated EGFR-mutated (exon 19 deletion or L858R) advanced non-small-cell lung cancer 1 to 1 between osimertinib 80 mg daily with pemetrexed and platinum chemotherapy, and osimertinib alone. The primary endpoint was investigator-assessed progression-free survival.\n\nIt is one of two 2023 and 2024 trials that beat osimertinib monotherapy, the other being MARIPOSA with amivantamab and lazertinib. Both ask the same unresolved question: whether intensifying first-line treatment for everybody is better than keeping a second option in reserve, and for which patients.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2023","url":"https://doi.org/10.1056/NEJMoa2306434"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37937763/"},{"label":"ClinicalTrials.gov NCT04035486","url":"https://clinicaltrials.gov/study/NCT04035486"}],"tags":["lung-evidence"],"related":["paper-flaura-nejm-2018","paper-cho-mariposa-amivantamab-lazertinib-nejm-2024","paper-osimertinib-nsclc-n-engl-j-med-2020"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc"],"sections":["targeted-therapy"],"technologies":[],"targets":["egfr"],"drugs":["osimertinib","pemetrexed","cisplatin","carboplatin"],"companies":["astrazeneca"],"institutions":[],"pathways":[],"terms":["driver-mutation","oncogene-addiction"],"trials":["flaura2"],"people":["david-planchard","pasi-janne"],"bottlenecks":["b-combination-space","b-resistance","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2023,"doi":"10.1056/NEJMoa2306434","pmid":"37937763","authors":"Planchard D, Jänne PA, Cheng Y, et al.","paperType":"rct","findings":["Investigator-assessed progression-free survival was significantly longer with osimertinib plus chemotherapy: hazard ratio for progression or death 0.62 (95 percent confidence interval 0.49 to 0.79).","557 patients underwent randomisation, 1 to 1, with exon 19 deletion or L858R mutations.","Europe PMC truncates the abstract after the P value for the primary endpoint, so the median progression-free survival figures and the safety numbers are not quoted here."],"whatItMeans":"Adding chemotherapy to osimertinib delays progression. Whether it extends life, and whether the same benefit could be had by giving the chemotherapy later to the patients who need it, is what the overall survival analysis and the registry watch on this roadmap are for.","caveats":["Progression-free survival by investigator assessment as the primary endpoint; overall survival was immature at this report.","Everyone in the combination arm receives platinum chemotherapy, including the substantial fraction who would have done well on osimertinib alone for years.","No direct comparison against MARIPOSA's amivantamab and lazertinib combination exists."],"changedPractice":true,"participants":557},"route":"/key-papers/paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023/","neighbours":{"paper":[{"id":"paper-cho-mariposa-amivantamab-lazertinib-nejm-2024","kind":"paper","name":"Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC","route":"/key-papers/paper-cho-mariposa-amivantamab-lazertinib-nejm-2024/"},{"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-osimertinib-nsclc-n-engl-j-med-2020","kind":"paper","name":"Overall Survival with Osimertinib in Untreated, EGFR -Mutated Advanced NSCLC","route":"/key-papers/paper-osimertinib-nsclc-n-engl-j-med-2020/"}],"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/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"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":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"}],"trial":[{"id":"flaura2","kind":"trial","name":"FLAURA2","route":"/trials/flaura2/"}],"person":[{"id":"david-planchard","kind":"person","name":"David Planchard","route":"/people/david-planchard/"},{"id":"pasi-janne","kind":"person","name":"Pasi A. Jänne","route":"/people/pasi-janne/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"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/"}]}}