{"entity":{"id":"paper-scher-affirm-enzalutamide-nejm-2012","kind":"paper","name":"AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapy","aka":["AFFIRM","Scher 2012 enzalutamide","MDV3100 AFFIRM"],"tldr":"Enzalutamide, an oral tablet that blocks the androgen receptor at several points at once, added nearly five months to median survival in men whose cancer had already been through chemotherapy. More than half had their PSA halve, against two percent on placebo.","summary":"Howard Scher and the AFFIRM investigators randomised 1,199 men with castration-resistant prostate cancer who had already had chemotherapy, in a 2 to 1 ratio, to 160 mg of enzalutamide daily or placebo. The trial was stopped at a planned interim analysis after 520 deaths.\n\nEnzalutamide came out of the Sawyers laboratory as a direct answer to the biology described in Chen 2004: a compound that stays an antagonist when the androgen receptor is abundant, and that also blocks nuclear translocation and DNA binding. AFFIRM is the clinical proof that the design brief was right. Every secondary endpoint moved in the same direction, which is unusual, and the effect size on prostate-specific antigen (54 percent against 2 percent) is among the largest in solid tumour oncology.","asOf":"2026-09-25","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/nejmoa1207506"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22894553/"},{"label":"ClinicalTrials.gov NCT00974311","url":"https://clinicaltrials.gov/study/NCT00974311"}],"tags":["prostate-evidence"],"related":["paper-beer-prevail-enzalutamide-nejm-2014","paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","paper-cou-aa-301-abiraterone-de-bono-nejm-2011","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","quality-of-life","radiographic-progression-free-survival"],"trials":[],"people":["howard-scher","karim-fizazi"],"bottlenecks":["b-resistance","b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/nejmoa1207506","pmid":"22894553","authors":"Scher HI, Fizazi K, Saad F, et al.","paperType":"rct","findings":["Median overall survival 18.4 months (95 percent confidence interval 17.3 to not yet reached) with enzalutamide against 13.6 months (11.3 to 15.8) with placebo; hazard ratio for death 0.63 (0.53 to 0.75; P less than 0.001).","A reduction in prostate-specific antigen of 50 percent or more in 54 percent against 2 percent (P less than 0.001).","Soft-tissue response rate 29 percent against 4 percent; quality-of-life response rate 43 percent against 18 percent (P less than 0.001 for both).","Radiographic progression-free survival 8.3 against 2.9 months (hazard ratio 0.40; P less than 0.001); time to first skeletal-related event 16.7 against 13.3 months (hazard ratio 0.69).","Seizures were reported in five patients (0.6 percent) receiving enzalutamide; fatigue, diarrhoea and hot flushes were more common."],"whatItMeans":"An oral drug that works after chemotherapy has failed, in a disease where the previous option was more chemotherapy. Together with abiraterone it moved castration-resistant prostate cancer from a chemotherapy disease to a hormonal one, and set up the sequencing questions the field is still arguing about.","caveats":["Placebo-controlled in a post-chemotherapy population, so it does not say how enzalutamide compares with abiraterone, cabazitaxel or radioligand therapy.","The 0.6 percent seizure rate excluded men with a history of seizure from the trial, so the real-world rate in unselected patients is not established here.","Cross-resistance with abiraterone was not tested; the CARD trial later showed that switching from one androgen receptor drug to the other is worse than moving to cabazitaxel."],"changedPractice":true,"participants":1199},"route":"/key-papers/paper-scher-affirm-enzalutamide-nejm-2012/","neighbours":{"paper":[{"id":"paper-cou-aa-301-abiraterone-de-bono-nejm-2011","kind":"paper","name":"COU-AA-301: abiraterone and increased survival in metastatic castration-resistant prostate cancer after docetaxel","route":"/key-papers/paper-cou-aa-301-abiraterone-de-bono-nejm-2011/"},{"id":"paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","kind":"paper","name":"Molecular determinants of resistance to antiandrogen therapy","route":"/key-papers/paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004/"},{"id":"paper-beer-prevail-enzalutamide-nejm-2014","kind":"paper","name":"PREVAIL: enzalutamide in metastatic prostate cancer before chemotherapy","route":"/key-papers/paper-beer-prevail-enzalutamide-nejm-2014/"},{"id":"paper-de-bono-tropic-cabazitaxel-lancet-2010","kind":"paper","name":"TROPIC: prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel","route":"/key-papers/paper-de-bono-tropic-cabazitaxel-lancet-2010/"}],"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":"psa","kind":"term","name":"PSA (prostate-specific antigen)","route":"/terms/psa/"},{"id":"quality-of-life","kind":"term","name":"Quality of life","route":"/terms/quality-of-life/"},{"id":"radiographic-progression-free-survival","kind":"term","name":"Radiographic progression-free survival (rPFS)","route":"/terms/radiographic-progression-free-survival/"}],"person":[{"id":"howard-scher","kind":"person","name":"Howard I. Scher","route":"/people/howard-scher/"},{"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-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/"}]}}