{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:41:48Z","timestamp":1790401308670,"version":"4.1.0"},"reference-count":20,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"25","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO ( ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> In period one, men with chemotherapy-na\u00efve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression (\u2265 25% increase and \u2265 2 ng\/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2018.77.9827","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T19:56:53Z","timestamp":1532116613000},"page":"2639-2646","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":155,"title":["Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment"],"prefix":"10.1200","volume":"36","author":[{"given":"Gerhardt","family":"Attard","sequence":"first","affiliation":[{"name":"Gerhardt Attard, The Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Michael Borre, Aarhus University Hospital, Aarhus, Denmark; Howard Gurney, Macquarie University, Sydney, New South Wales, Australia; Yohann Loriot, Gustave Roussy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U981, University of Paris Saclay, Villejuif, France; Corina Andresen-Daniil, Ranjith Kalleda, and Trinh Pham, Pfizer, New York, NY; and Mary-Ellen..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Borre","sequence":"additional","affiliation":[{"name":"Gerhardt Attard, The Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Michael Borre, Aarhus University Hospital, Aarhus, Denmark; Howard Gurney, Macquarie University, Sydney, New South Wales, Australia; Yohann Loriot, Gustave Roussy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U981, University of Paris Saclay, Villejuif, France; Corina Andresen-Daniil, Ranjith Kalleda, and Trinh Pham, Pfizer, New York, NY; and Mary-Ellen..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Gurney","sequence":"additional","affiliation":[{"name":"Gerhardt Attard, The Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Michael Borre, Aarhus University Hospital, Aarhus, Denmark; Howard Gurney, Macquarie University, Sydney, New South Wales, Australia; Yohann Loriot, Gustave Roussy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U981, University of Paris Saclay, Villejuif, France; Corina Andresen-Daniil, Ranjith Kalleda, and Trinh Pham, Pfizer, New York, NY; and Mary-Ellen..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohann","family":"Loriot","sequence":"additional","affiliation":[{"name":"Gerhardt Attard, The Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Michael Borre, Aarhus University Hospital, Aarhus, Denmark; Howard Gurney, Macquarie University, Sydney, New South Wales, Australia; Yohann Loriot, Gustave Roussy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U981, University of Paris Saclay, Villejuif, France; Corina Andresen-Daniil, Ranjith Kalleda, and Trinh Pham, Pfizer, New York, NY; and Mary-Ellen..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Andresen-Daniil","sequence":"additional","affiliation":[{"name":"Gerhardt Attard, The Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Michael Borre, Aarhus University Hospital, Aarhus, Denmark; Howard Gurney, Macquarie University, Sydney, New South Wales, Australia; Yohann Loriot, Gustave Roussy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U981, University of Paris Saclay, Villejuif, France; Corina Andresen-Daniil, Ranjith Kalleda, and Trinh Pham, Pfizer, New York, NY; and Mary-Ellen..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjith","family":"Kalleda","sequence":"additional","affiliation":[{"name":"Gerhardt Attard, The Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Michael Borre, Aarhus University Hospital, Aarhus, Denmark; Howard Gurney, Macquarie University, Sydney, New South Wales, Australia; Yohann Loriot, Gustave Roussy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U981, University of Paris Saclay, Villejuif, France; Corina Andresen-Daniil, Ranjith Kalleda, and Trinh Pham, Pfizer, New York, NY; and Mary-Ellen..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinh","family":"Pham","sequence":"additional","affiliation":[{"name":"Gerhardt Attard, The Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Michael Borre, Aarhus University Hospital, Aarhus, Denmark; Howard Gurney, Macquarie University, Sydney, New South Wales, Australia; Yohann Loriot, Gustave Roussy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U981, University of Paris Saclay, Villejuif, France; Corina Andresen-Daniil, Ranjith Kalleda, and Trinh Pham, Pfizer, New York, NY; and Mary-Ellen..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Ellen","family":"Taplin","sequence":"additional","affiliation":[{"name":"Gerhardt Attard, The Institute of Cancer Research and the Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Michael Borre, Aarhus University Hospital, Aarhus, Denmark; Howard Gurney, Macquarie University, Sydney, New South Wales, Australia; Yohann Loriot, Gustave Roussy, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U981, University of Paris Saclay, Villejuif, France; Corina Andresen-Daniil, Ranjith Kalleda, and Trinh Pham, Pfizer, New York, NY; and Mary-Ellen..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the PLATO collaborators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1405095"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71205-7"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.11.006"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.05.005"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3980"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.9749"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009448"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1220"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac9511"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.012"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3630"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.4487"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/63.3.655"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014618"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209096"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.08.020"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt136"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt138"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.05.038"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx155"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2018.77.9827","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T10:21:16Z","timestamp":1653819676000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2018.77.9827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,1]]},"references-count":20,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2018,9,1]]}},"alternative-id":["10.1200\/JCO.2018.77.9827"],"URL":"https:\/\/doi.org\/10.1200\/jco.2018.77.9827","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,1]]},"assertion":[{"value":"2018-07-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}