Ian D Davis1, Andrew J Martin1, Martin R Stockler1, Stephen Begbie1, Kim N Chi1, Simon Chowdhury1, Xanthi Coskinas1, Mark Frydenberg1, Wendy E Hague1, Lisa G Horvath1, Anthony M Joshua1, Nicola J Lawrence1, Gavin Marx1, John McCaffrey1, Ray McDermott1, Margaret McJannett1, Scott A North1, Francis Parnis1, Wendy Parulekar1, David W Pook1, M Neil Reaume1, Shahneen K Sandhu1, Alvin Tan1, T Hsiang Tan1, Alastair Thomson1, Emily Tu1, Francisco Vera-Badillo1, Scott G Williams1, Sonia Yip1, Alison Y Zhang1, Robert R Zielinski1, Christopher J Sweeney1. 1. From Monash University (I.D.D., M.F., D.W.P.), Eastern Health (I.D.D.), Australian Urology Associates (M.F.), Monash Health (D.W.P.), and the Peter MacCallum Cancer Centre and the University of Melbourne (S.K.S., S.G.W.), Melbourne, VIC, the National Health and Medical Research Council Clinical Trials Centre, University of Sydney (A.J.M., M.R.S., X.C., W.E.H., E.T., S.Y., A.Y.Z.), the Chris O'Brien Lifehouse (M.R.S., L.G.H., A.Y.Z.), the University of Sydney (L.G.H., G.M.), Royal Prince Alfred Hospital (L.G.H.), Kinghorn Cancer Centre, St. Vincent's Hospital, and Garvan Institute of Medical Research (A.M.J.), Macquarie University (A.Y.Z.), and Western Sydney University (R.R.Z.), Sydney, Concord Cancer Centre, Concord Repatriation General Hospital, Concord, NSW (M.R.S.), Port Macquarie Base Hospital and Mid North Coast Cancer Institute Port Macquarie, Port Macquarie, NSW (S.B.), Sydney Adventist Hospital, Wahroonga, NSW (G.M.), the ANZUP Cancer Trials Group, Camperdown, NSW (M.M.), the Adelaide Cancer Centre and the University of Adelaide (F.P.) and the Royal Adelaide Hospital (T.H.T.), Adelaide, SA, and Orange Health Service, Central West Cancer Care Centre, Orange, NSW (R.R.Z.) - all in Australia; BC Cancer and the University of British Columbia, Vancouver (K.N.C.), the Cross Cancer Institute and the University of Alberta, Edmonton (S.A.N.), Canadian Cancer Trials Group, Queen's University (W.P., F.V.-B.), and the Kingston Health Sciences Center (F.V.-B.), Kingston, ON, and the University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (M.N.R.) - all in Canada; Guy's and St. Thomas' NHS Foundation Trust Biomedical Research Centre, Cancer Research UK and King's College London, and Sarah Cannon Research UK, London (S.C.), and the Royal Cornwall Hospital, Truro (A. Thomson) - all in the United Kingdom; Auckland City Hospital, Auckland (N.J.L.), and the Waikato District Health Board, Hamilton (A. Tan) - both in New Zealand; Cancer Trials Ireland (J.M., R.M.), Mater Misericordiae University Hospital (J.M.), and St. Vincent's University Hospital and University College Dublin (R.M.D.) - all in Dublin; and Dana-Farber Cancer Institute and Harvard Medical School (C.J.S.) - both in Boston.
Abstract
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. METHODS: 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. RESULTS: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. CONCLUSIONS: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.).
RCT Entities:
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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.).
Authors: Wanling Xie; Meredith M Regan; Marc Buyse; Susan Halabi; Philip W Kantoff; Oliver Sartor; Howard Soule; Donald Berry; Noel Clarke; Laurence Collette; Anthony D'Amico; Richard De Abreu Lourenco; James Dignam; Mario Eisenberger; Nicholas James; Karim Fizazi; Silke Gillessen; Yohann Loriot; Nicolas Mottet; Wendy Parulekar; Howard Sandler; Daniel E Spratt; Matthew R Sydes; Bertrand Tombal; Scott Williams; Christopher J Sweeney Journal: J Clin Oncol Date: 2020-06-18 Impact factor: 44.544
Authors: Myrto Boukovala; Nicholas Spetsieris; Justin A Weldon; Alexandros Tsikkinis; Anh Hoang; Ana Aparicio; Shi-Ming Tu; John C Araujo; Amado J Zurita; Paul G Corn; Lance Pagliaro; Jeri Kim; Jennifer Wang; Sumit K Subudhi; Nizar M Tannir; Christopher J Logothetis; Patricia Troncoso; Sijin Wen; Eleni Efstathiou Journal: Eur J Cancer Date: 2020-01-24 Impact factor: 9.162
Authors: Emmanuel S Antonarakis; Jun Luo; Andrew J Armstrong; Landon C Brown; Changxue Lu Journal: Prostate Cancer Prostatic Dis Date: 2020-02-24 Impact factor: 5.554