{"entity":{"id":"flyer","kind":"trial","name":"FLYER","aka":["Four versus six cycles of CHOP with rituximab","FLYER trial"],"tldr":"Young people with early, low-risk aggressive lymphoma got two fewer rounds of chemotherapy and did just as well, with about a third fewer side effects recorded.","summary":"FLYER asked the de-escalation question that matters most to a 30-year-old: how little chemotherapy is enough. It enrolled people aged 18 to 60 with stage I or II aggressive B-cell non-Hodgkin lymphoma, a normal serum lactate dehydrogenase, performance status 0 or 1 and no bulky mass, at 138 sites in Germany, Denmark, Israel, Italy and Norway, and randomised them between six cycles of R-CHOP and four cycles of CHOP with six doses of rituximab.\n\nAt a median follow-up of 66 months, three-year progression-free survival with four cycles was 96 per cent (95 per cent confidence interval 94 to 99), 3 percentage points better than six cycles, which established non-inferiority against a margin of minus 5.5 points. The toxicity difference is the point of the trial: 294 haematological and 1,036 non-haematological adverse events 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.\n\nFLYER is why a young person with favourable limited-stage disease is now routinely offered four cycles rather than six, and why the conversation about radiotherapy in that setting is separate from the conversation about chemotherapy duration: no radiotherapy was planned in either arm except for testicular lymphoma.","status":"positive","asOf":"2026-10-01","links":[{"label":"ClinicalTrials.gov NCT00278421","url":"https://clinicaltrials.gov/study/NCT00278421"},{"label":"Lancet 2019","url":"https://doi.org/10.1016/S0140-6736(19)33008-9"}],"tags":["lymphoma-evidence"],"related":[],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["chemotherapy","immunotherapy"],"technologies":["cytotoxic-chemotherapy","monoclonal-antibody"],"targets":[],"drugs":["rituximab","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":["r-chop","non-inferiority","ipi-score"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":["paper-flyer-four-vs-six-cycles-r-chop-lancet-2019"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00278421","phase":"3","setting":"Aged 18 to 60 with stage I or II aggressive B-cell lymphoma, normal lactate dehydrogenase, no bulk: four cycles of R-CHOP with six doses of rituximab against six cycles of R-CHOP","sponsor":"German High-Grade Non-Hodgkin's Lymphoma Study Group","result":"Three-year progression-free survival 96 per cent with four cycles of R-CHOP plus two extra rituximab doses, non-inferior to six cycles, with roughly a quarter fewer adverse events.","started":"2005-11","yearReported":2019,"enrolled":588,"enrolledBasis":"analysed","enrolledNote":"The registry records 592 enrolled; four patients withdrew consent before treatment, so the intention-to-treat analysis covers 588.","outcomes":[{"endpoint":"Progression-free survival at 3 years","primary":true,"unit":"%","arms":[{"name":"Four cycles R-CHOP plus two rituximab","n":293,"value":96},{"name":"Six cycles R-CHOP","n":295,"note":"3 percentage points lower; the one-sided 95 per cent confidence interval for the difference had a lower limit of 0 per cent"}],"source":"https://doi.org/10.1016/S0140-6736(19)33008-9"}],"replication":"Consistent with the direction of the earlier MInT and RICOVER-60 work from the same group; no independent randomised repeat."},"route":"/trials/flyer/","neighbours":{"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/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"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":"ipi-score","kind":"term","name":"International Prognostic Index (IPI)","route":"/terms/ipi-score/"},{"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/"}],"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/"}],"paper":[{"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)","route":"/key-papers/paper-flyer-four-vs-six-cycles-r-chop-lancet-2019/"}],"trial":[{"id":"polarix","kind":"trial","name":"POLARIX","route":"/trials/polarix/"}],"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/"}]}}