{"entity":{"id":"paper-beer-prevail-enzalutamide-nejm-2014","kind":"paper","name":"PREVAIL: enzalutamide in metastatic prostate cancer before chemotherapy","aka":["PREVAIL","Beer 2014 enzalutamide chemotherapy-naive"],"tldr":"The same drug given before chemotherapy rather than after it. At one year, 65 percent of men on enzalutamide had no sign of the cancer growing on scans, against 14 percent on placebo, and the need for chemotherapy was pushed a long way back.","summary":"Tomasz Beer and the PREVAIL investigators randomised 1,717 chemotherapy-naive men with metastatic castration-resistant prostate cancer to 160 mg of enzalutamide daily or placebo, with radiographic progression-free survival and overall survival as co-primary endpoints. The study was stopped at a planned interim analysis after 540 deaths.\n\nPREVAIL did for enzalutamide what COU-AA-302 did for abiraterone: it moved the drug in front of chemotherapy. The two results together are the reason a man diagnosed with castration-resistant disease today is far more likely to be offered a tablet than an infusion, and the reason the sequencing question (which tablet, then what) became the central practical problem of the disease.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2014","url":"https://doi.org/10.1056/nejmoa1405095"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24881730/"},{"label":"ClinicalTrials.gov NCT01212991","url":"https://clinicaltrials.gov/study/NCT01212991"}],"tags":["prostate-evidence"],"related":["paper-scher-affirm-enzalutamide-nejm-2012","paper-abiraterone-acetate-prostate-n-engl-j-med-2013","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal","targeted-therapy"],"technologies":[],"targets":["androgen-receptor"],"drugs":["enzalutamide"],"companies":["astellas","pfizer"],"institutions":[],"pathways":[],"terms":["castration-resistance","psa","radiographic-progression-free-survival","metastasis-free-survival"],"trials":[],"people":["johann-de-bono","karim-fizazi"],"bottlenecks":["b-resistance","b-combination-space"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2014,"doi":"10.1056/nejmoa1405095","pmid":"24881730","authors":"Beer TM, Armstrong AJ, Rathkopf DE, et al.","paperType":"rct","findings":["Radiographic progression-free survival at 12 months 65 percent with enzalutamide against 14 percent with placebo (hazard ratio 0.19, 95 percent confidence interval 0.15 to 0.23; P less than 0.001).","626 of the enzalutamide patients (72 percent) against 532 (63 percent) on placebo were alive at the data-cutoff; hazard ratio for death 0.71 (0.60 to 0.84; P less than 0.001).","Time until initiation of cytotoxic chemotherapy hazard ratio 0.35; time until first skeletal-related event hazard ratio 0.72.","Complete or partial soft-tissue response in 59 percent against 5 percent; decline of at least 50 percent in prostate-specific antigen in 78 percent against 3 percent (P less than 0.001 for all comparisons).","Fatigue and hypertension were the most common clinically relevant adverse events."],"whatItMeans":"The trial that made an androgen receptor inhibitor the usual first treatment for castration-resistant prostate cancer, and that delayed chemotherapy by a long margin for most men. Its effect sizes are why later trials in this setting are judged against a hazard ratio near 0.7 for survival.","caveats":["Placebo-controlled, so it does not compare enzalutamide with abiraterone or with chemotherapy given at the same point.","Most of the men in PREVAIL had not previously received an androgen receptor pathway inhibitor in hormone-sensitive disease; today most have, which makes the trial's population historical.","Radiographic progression-free survival at 12 months is a landmark analysis and is sensitive to the imaging schedule the protocol specified."],"changedPractice":true,"participants":1717},"route":"/key-papers/paper-beer-prevail-enzalutamide-nejm-2014/","neighbours":{"paper":[{"id":"paper-abiraterone-acetate-prostate-n-engl-j-med-2013","kind":"paper","name":"Abiraterone in metastatic prostate cancer without previous chemotherapy","route":"/key-papers/paper-abiraterone-acetate-prostate-n-engl-j-med-2013/"},{"id":"paper-scher-affirm-enzalutamide-nejm-2012","kind":"paper","name":"AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapy","route":"/key-papers/paper-scher-affirm-enzalutamide-nejm-2012/"}],"roadmap":[{"id":"prostate-roadmap","kind":"roadmap","name":"Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch","route":"/roadmaps/prostate-roadmap/"}],"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"section":[{"id":"hormonal","kind":"section","name":"Hormonal Therapy","route":"/fronts/hormonal/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"}],"drug":[{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"}],"company":[{"id":"astellas","kind":"company","name":"Astellas","route":"/companies/astellas/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"term":[{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"metastasis-free-survival","kind":"term","name":"Metastasis-free survival (MFS)","route":"/terms/metastasis-free-survival/"},{"id":"psa","kind":"term","name":"PSA (prostate-specific antigen)","route":"/terms/psa/"},{"id":"radiographic-progression-free-survival","kind":"term","name":"Radiographic progression-free survival (rPFS)","route":"/terms/radiographic-progression-free-survival/"}],"person":[{"id":"johann-de-bono","kind":"person","name":"Johann de Bono","route":"/people/johann-de-bono/"},{"id":"karim-fizazi","kind":"person","name":"Karim Fizazi","route":"/people/karim-fizazi/"}],"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/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}