{"entity":{"id":"paper-enzamet-n-engl-j-med-2019","kind":"paper","name":"Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer","aka":[],"tldr":"Published report from the ENZAMET trial registered as NCT02446405, in New England Journal of Medicine (2019), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer.\n\nMethods: In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events.\n\nResults: A total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P = 0.002). Kaplan-Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P<0.001) and in clinical progression-free survival (167 and 320 events, respectively; hazard ratio, 0.40; P<0.001). Treatment discontinuation due to adverse events was more frequent in the enzalutamide group than in the standard-care group (33 events and 14 events, respectively). Fatigue was more common in the enzalutamide group; seizures occurred in 7 patients in the enzalutamide group (1%) and in no patients in the standard-care group.\n\nConclusions: Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel. (Funded by Astellas Scientific and Medical Affairs and others; ENZAMET (ANZUP 1304) ANZCTR number, ACTRN12614000110684; ClinicalTrials.gov number, NCT02446405; and EU Clinical Trials Register number, 2014-003190-42.).\n\nIndexed on Europe PMC as PubMed record 31157964 (DOI 10.1056/nejmoa1903835). Its abstract cites the registry id NCT02446405, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2019","url":"https://doi.org/10.1056/nejmoa1903835"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31157964/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/31157964"},{"label":"ClinicalTrials.gov NCT02446405","url":"https://clinicaltrials.gov/study/NCT02446405"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["enzamet"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2019,"doi":"10.1056/nejmoa1903835","pmid":"31157964","authors":"Davis ID, Martin AJ, Stockler MR, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02446405 with the most citations, so it is the natural first reading for anyone following the ENZAMET trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-enzamet-n-engl-j-med-2019/","neighbours":{"trial":[{"id":"enzamet","kind":"trial","name":"ENZAMET","route":"/trials/enzamet/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}