{"entity":{"id":"paper-flyer-four-vs-six-cycles-r-chop-lancet-2019","kind":"paper","name":"Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER)","aka":["FLYER","Poeschel 2019"],"tldr":"Young people with early, low-risk aggressive lymphoma did just as well with four rounds of chemotherapy as with six, and had roughly a quarter fewer side effects.","summary":"An open-label, international, randomised phase 3 non-inferiority trial at 138 sites in Denmark, Germany, Israel, Italy and Norway. It enrolled patients aged 18 to 60 with stage I to II aggressive B-cell non-Hodgkin lymphoma, normal serum lactate dehydrogenase, performance status 0 to 1 and no bulky disease, and randomised them between six cycles of R-CHOP and four cycles of CHOP with six applications of rituximab. No radiotherapy was planned except for testicular lymphoma.\n\n592 patients were enrolled between 2 December 2005 and 7 October 2016, 295 to six cycles and 297 to four; four withdrew consent before treatment, leaving 588 in the intention-to-treat analysis. After a median follow-up of 66 months (interquartile range 42 to 100), three-year progression-free survival in the four-cycle group was 96 per cent (95 per cent confidence interval 94 to 99), 3 percentage points better than six cycles, with a lower limit of the one-sided 95 per cent confidence interval for the difference of 0 per cent, which demonstrated non-inferiority against a margin of minus 5.5 per cent.","asOf":"2026-10-01","links":[{"label":"Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(19)33008-9"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31868632/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31868632"}],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["chemotherapy"],"technologies":[],"targets":[],"drugs":["rituximab","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":["r-chop","non-inferiority"],"trials":["flyer"],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"Lancet","year":2019,"doi":"10.1016/S0140-6736(19)33008-9","pmid":"31868632","authors":"Poeschel V, Held G, Ziepert M, et al.","paperType":"rct","findings":["Three-year progression-free survival with four cycles of R-CHOP plus two further rituximab doses was 96 per cent (95 per cent confidence interval 94 to 99), 3 percentage points better than six cycles.","Non-inferiority was demonstrated against a margin of minus 5.5 per cent.","294 haematological and 1,036 non-haematological adverse events were documented in the four-cycle group against 426 and 1,280 in the six-cycle group.","Two patients died during study therapy, both in the six-cycle group."],"whatItMeans":"Four cycles rather than six for young patients with limited-stage, low-risk aggressive B-cell lymphoma. The saving is two cycles of anthracycline and vincristine in people who will live for decades afterwards.","caveats":["Restricted to patients aged 18 to 60 with normal lactate dehydrogenase, no bulk and performance status 0 to 1: the result does not transfer to higher-risk limited-stage disease.","Recruitment took eleven years, and the chemotherapy standard did not change in that time, but supportive care did.","Radiotherapy was not part of either arm, so the trial does not speak to combined-modality strategies."],"changedPractice":true,"participants":588},"route":"/key-papers/paper-flyer-four-vs-six-cycles-r-chop-lancet-2019/","neighbours":{"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"}],"drug":[{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"term":[{"id":"non-inferiority","kind":"term","name":"Non-inferiority trial","route":"/terms/non-inferiority/"},{"id":"r-chop","kind":"term","name":"R-CHOP (lymphoma chemoimmunotherapy)","route":"/terms/r-chop/"}],"trial":[{"id":"flyer","kind":"trial","name":"FLYER","route":"/trials/flyer/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}]}}