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N Engl J Med. 2018 Apr 12;378(15):1408-1418. doi: 10.1056/NEJMoa1715546. Epub 2018 Feb 8.

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.

Collaborators (451)

Horvath L, Nott L, Mathlum M, Coward J, Ng S, Epstein R, Tran B, Guminski A, Bastick P, Pittman K, Tan H, Wei C, Kukard C, Nasser E, Parente P, Marx G, Krainer M, Loidl W, Hutterer G, Tombal B, Sautois B, Werbrouck P, Roumeguère T, Ameye F, Joniau S, Lumen N, Renaud P, North S, Chin J, Barkin J, Carmel M, Casey R, Gleave M, Klotz L, Ouellette P Jr, Eiley D, Hamilton R, Attwell A, Lacombe L, Wood L, Aaron L, Abdelsalam M, Canil C, Ellard S, Webster T, Reiman A, Flax S, Vrabec G, Bladou F, Donnelly B, Giddens J, Leung W, Shayegan B, Lukka H, Simard J, Zadra J, Archambault R, Melichar B, Stahalova V, Stanek R, Matouskova M, Pavlik I, Sochor M, Jarolím L, Zachoval M, Klecka J, Brasso K, Harving N, Holm-Nielsen A, Poulsen M, Taari K, Tammela T, Boström P, Ronkainen H, Marttila T, Vincendeau S, Berdah JF, Villers A, Pfister C, Flechon A, Mouillet G, Bompas E, Delva R, Joly F, Beuzeboc P, Eymard JC, Colombel M, Ferrero JM, Gravis G, Krakowski I, Voog E, Barthelemy P, Robert G, Priou F, Barry-Delongchamps N, Larré S, Theodore C, Azzouzi AR, Deville JL, Linassier C, Mahammedi H, Houédé N, Artignan X, Feyerabend S, Gleissner J, von Klot C, Stöckle M, van Essen J, Ritter M, Stenzl A, Grimm MO, Suttmann H, Rodemer G, Steuber T, Rudolph R, Tsaur I, Bögemann M, Klotz T, Thomas C, Reichle A, Huebner A, Koenig F, Spiegelhalder P, Bismarck E, Hellmis E, Carl S, Strauss A, Berse M, Kretz T, Zimmermann U, Hammerer P, Lehmann J, Geiges G, Machtens S, Katona F, Szilágyi L, Kulcsár D, Lakatos Á, Géczi L, Berger R, Sella A, Nativ O, Frank S, Rosenbaum E, Peer A, Keizman D, Stein A, Sarid D, Sternberg C, Bracarda S, Paglino C, Gallucci M, Alabiso O, Bertolini A, Cianci C, Ciuffreda L, Rocco F, De Giorgi U, Boccardo F, Cappuzzo F, Emarcora P, Battaglia M, Scagliotti G, Nolè F, Cicalese V, Sakai H, Tsunemori H, Maruyama S, Suzuki H, Kawano Y, Heshine K, Fukumori T, Mizokami A, Tamada S, Tsumura H, Tozawa K, Yamaguchi A, Arai G, Tsuchiya T, Matsubara A, Matsubara N, Furukawa J, Azumi M, Uemura H, Kinoshita H, Igawa T, Tanabe K, Kasahara T, Saito S, Sugimoto T, Iijima K, Matsumoto H, Narita S, Hara I, Kobayashi H, Takahashi A, de Wildt M, Beeker A, Hamberg P, Mulders P, Helgason H, Vergunst H, Roeleveld T, Beaven A, Gilling P, Buchan N, Nixon T, Angelsen A, Heinrich D, Zurawski B, Milecki P, Walaszkowska-Czyz A, Jassem J, Humanski P, Darewicz B, Pikiel J, Drewa T, Sosnowski M, Radziszewski P, Slojewski M, Zdrojowy R, Ciurescu D, Jinga V, Toganel C, Udrea A, Herzal A, Semenov A, Alekseev B, Ivanov S, Kopyltsov E, Kheyfets V, Varlamov S, Kovalenko R, Cheporov S, Karyakin O, Izmailov A, Kulikov E, Khvorostenko D, Gorelov A, Matveev V, Kopp M, Goncalves F, Sokol R, Kliment J, Knazik R, Brezovsky M, Chung BH, Lee HM, Choi YD, Ha HK, Kwak C, Byun SS, Kim CS, Kim CI, Kang TW, Moon G, Kwon TG, García-Donás J, Maroto JP, Arranz JA, Carles J, Castellano D, Perez Gracia JL, Iborra I, Barretina Ginesta MP, Font A, Gallardo E, Gonzalez del Alba A, Casinnello J, Rubio G, Gonzalez Larriba JL, Carballido J, Juarez A, Miñana B, Ribal MJ, Ferrer C, Angulo J, Rios Gonzalez E, Medina R, Chantada V, Guttierez JL, Sanchez E, Lara P, Llarena R, Gomez Veiga F, Damber JE, Häggman M, Widmark A, Andren O, Kjellman A, Wu T, Chung HJ, Wu HC, Ou YC, Chiang PH, Pang ST, Huang CY, Mills J, Jones R, McInerney P, Attard G, Malik Z, Pandha H, Mazhar D, Bottomley D, Button M, Beesley S, Nabi G, Sayers I, Parikh O, Crabb S, Wagstaff J, Falconer A, Aggarwal R, Shore N, Antonarakis ES, Liu G, Sieber P, Tutrone R Jr, Belkoff L, Hainsworth J, Higano C, Twardowski P, Rathkopf D, Given R, Karlin G, Lara P Jr, Nordquist L, Srinivas S, Dakhil S, Bracken RB, Westenfelder K, Frankel J, Brand T, Drakaki A, Sonpavde G, Tejwani S, Cook D, Israel A, Dato P, Perzin A, Williams T, Alter R, Gingrich J, Uchio E, Williams J, Zibelman M, Prasad S, Karsh L, Patsias G, Savage S, Van Veldhuizen P, Miller L, Pieczonka C, Kambhampati S, Deguenther M, Keller L III, Omarbasha B, Clark W, Bertram R, Saslawsky M, Hauke R, Myrick S, Ghaddar H, Foreno L, Forero G, Doshi G, Fleming M, Troner M, Shaffer D, Vogelzang N, Hirsch B, Schnadig I, Bailen J, Gittelman M, Goldfischer E, Fisher H, Grable M, Corn P, Lim E, Cosgriff T, Chu F, Acs P, Reeves J Jr, Stein M, Al-Janadi A, Siegel R, Patel K, Kella N, Willard TB, Gatrell B, Schiffman Z, Bidair M, Ornstein D, Bylow K, Agrawal M, Suh R, Busby JE, Bardot S, Taylor J, Wolk F, Courtney K, Vaishampayan U, Sharifi R, Hoimes C, Harris R, Nickols N, Rosales J, Wrenn J, Goueli B, Dorff T, Yee D, David R, Bianco F, Henry E, Jaslowski A, Mannuel H, Krejci K, Gervasi L, Clement J, Bernstein G, Somer B, Lipsitz D, Heron S, Nemoy N, Rosenberg S, Miller A, Shetty S, Weckstein D, Salazar M, Margolis E, Katz A, Renzuli J II, Tan W, Van Echo D, Haluschak J, Showel J, Schmidt W Jr, Sharma S, Hancock M, Morris D, Tebyani N, Armas A, Tarter T, Balaji KC, Franks M, Williams R, Snoy F, Pachynski R, Ahaghotu C, Kemeny M.

Author information

1
From the Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (M.R.S.); Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal (F.S.); Guy's, King's and St. Thomas' Hospitals, Great Maze Pond, London (S.C.); Georges Pompidou Hospital, Paris (S.O.); University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany (B.A.H.); Veterans Affairs Portland Health Care System, Portland, and Knight Cancer Institute, Oregon Health and Science University, Portland (J.N.G.); Spanish National Cancer Research Center, Madrid, and Hospitales Universitarios Virgen de la Victoria y Regional, Institute of Biomedical Research in Malaga, Malaga - both in Spain (D.O.); Centre for Personalised Nanomedicine, University of Queensland, Brisbane, Australia (P.N.M.); St. Mary's Hospital of Catholic University, Seoul, South Korea (J.Y.L.); Yokohama City University Medical Center, Yokohama, Japan (H.U.); Janssen Research and Development, Los Angeles (A.L.-G., G.C.T., B.M.E., Y.S., Y.C.P., W.R.R., M.K.Y.); and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco (E.J.S.).

Abstract

BACKGROUND:

Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.

METHODS:

We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.

RESULTS:

A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%).

CONCLUSIONS:

Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204 .).

PMID:
29420164
DOI:
10.1056/NEJMoa1715546
[Indexed for MEDLINE]
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