Increased survival with enzalutamide in prostate cancer after chemotherapy
Howard I Scher, Karim Fizazi, Fred Saad, Mary-Ellen Taplin, Cora N Sternberg, Kurt Miller, Ronald de Wit, Peter Mulders, Kim N Chi, Neal D Shore, Andrew J Armstrong, Thomas W Flaig, Aude Fléchon, Paul Mainwaring, Mark Fleming, John D Hainsworth, Mohammad Hirmand, Bryan Selby, Lynn Seely, Johann S de Bono, AFFIRM Investigators, C Alasino, S Bella, S Carraro, M Geist, E Abdi, S Begbie, K Briscoe, Ian Davis, A Dowling, V Ganju, H Gurney, E Hovey, S Ng, M Nottage, M Rosenthal, M Stockler, T H Tan, S Wong, R Young, M Krainer, W Loidl, J P Machiels, J Mebis, V Renard, H Dumez, F Van Aelst, P Werbrouck, S Ellard, A Joshua, P Karakiewicz, L Lacombe, J B Lattouf, J Michels, S Mukherjee, D Ruether, P Venner, E Winquist, L Wood, O Aren, P Gonzalez, P Pastor, I Baumgaertner, P Beuzeboc, E Bompas, H Boyle, M Colombel, R Delva, J C Eymard, G Gravis, A Guillot, N Houédé, F Joly, R Kaphan, Y Loriot, S Oudard, F Priou, S Tartas, C Theodore, J-M Tourani, E Voog, M Bögemann, B Hadaschik, P Hammerer, A Heidenreich, W Holzer, A Merseburger, A Stenzl, T Steuber, H Suttmann, L Trojan, M Wirth, L Cerbone, P Conte, R Passalacqua, M Tucci, W Gerritsen, J Jassem, E Kalinka-Warzocha, J Olubiec, R De Bruyne, J Malan, D Vorobiof, J Bellmunt, J Carles, I Durán, A Font, I Gil-Bazo, J P Maroto, A Bahl, A Choudhury, P Hoskin, N James, R Jones, D Mazhar, J O'Sullivan, H Payne, I Pedley, A Protheroe, J Waxman, A Zivi, B Alexander, L Appleman, J Aragon-Ching, E Arrowsmith, V Assikis, T Beer, W Berry, G Bolger, A Bryce, G Bubley, G Chatta, S Denmeade, H Deshpande, T Dorff, M Galsky, D George, R Giudice, M Glode, A-R Golshayan, O Goodman, J Graff, L Green, R Green, N Haas, C Higano, T Hutson, M Kohli, G Liu, J May, D Mendelson, J Picus, R Pili, E Posadas, C Redfern, M Rettig, C Ryan, M Scholz, N Sharifi, J Sosman, S Srinivas, S Tagawa, P Twardowski, U Vaishampayan, Y-N Wong, Howard I Scher, Karim Fizazi, Fred Saad, Mary-Ellen Taplin, Cora N Sternberg, Kurt Miller, Ronald de Wit, Peter Mulders, Kim N Chi, Neal D Shore, Andrew J Armstrong, Thomas W Flaig, Aude Fléchon, Paul Mainwaring, Mark Fleming, John D Hainsworth, Mohammad Hirmand, Bryan Selby, Lynn Seely, Johann S de Bono, AFFIRM Investigators, C Alasino, S Bella, S Carraro, M Geist, E Abdi, S Begbie, K Briscoe, Ian Davis, A Dowling, V Ganju, H Gurney, E Hovey, S Ng, M Nottage, M Rosenthal, M Stockler, T H Tan, S Wong, R Young, M Krainer, W Loidl, J P Machiels, J Mebis, V Renard, H Dumez, F Van Aelst, P Werbrouck, S Ellard, A Joshua, P Karakiewicz, L Lacombe, J B Lattouf, J Michels, S Mukherjee, D Ruether, P Venner, E Winquist, L Wood, O Aren, P Gonzalez, P Pastor, I Baumgaertner, P Beuzeboc, E Bompas, H Boyle, M Colombel, R Delva, J C Eymard, G Gravis, A Guillot, N Houédé, F Joly, R Kaphan, Y Loriot, S Oudard, F Priou, S Tartas, C Theodore, J-M Tourani, E Voog, M Bögemann, B Hadaschik, P Hammerer, A Heidenreich, W Holzer, A Merseburger, A Stenzl, T Steuber, H Suttmann, L Trojan, M Wirth, L Cerbone, P Conte, R Passalacqua, M Tucci, W Gerritsen, J Jassem, E Kalinka-Warzocha, J Olubiec, R De Bruyne, J Malan, D Vorobiof, J Bellmunt, J Carles, I Durán, A Font, I Gil-Bazo, J P Maroto, A Bahl, A Choudhury, P Hoskin, N James, R Jones, D Mazhar, J O'Sullivan, H Payne, I Pedley, A Protheroe, J Waxman, A Zivi, B Alexander, L Appleman, J Aragon-Ching, E Arrowsmith, V Assikis, T Beer, W Berry, G Bolger, A Bryce, G Bubley, G Chatta, S Denmeade, H Deshpande, T Dorff, M Galsky, D George, R Giudice, M Glode, A-R Golshayan, O Goodman, J Graff, L Green, R Green, N Haas, C Higano, T Hutson, M Kohli, G Liu, J May, D Mendelson, J Picus, R Pili, E Posadas, C Redfern, M Rettig, C Ryan, M Scholz, N Sharifi, J Sosman, S Srinivas, S Tagawa, P Twardowski, U Vaishampayan, Y-N Wong
Abstract
Background: Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor-signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy.
Methods: In our phase 3, double-blind, placebo-controlled trial, we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity. We randomly assigned them, in a 2:1 ratio, to receive oral enzalutamide at a dose of 160 mg per day (800 patients) or placebo (399 patients). The primary end point was overall survival.
Results: The study was stopped after a planned interim analysis at the time of 520 deaths. The median overall survival was 18.4 months (95% confidence interval [CI], 17.3 to not yet reached) in the enzalutamide group versus 13.6 months (95% CI, 11.3 to 15.8) in the placebo group (hazard ratio for death in the enzalutamide group, 0.63; 95% CI, 0.53 to 0.75; P<0.001). The superiority of enzalutamide over placebo was shown with respect to all secondary end points: the proportion of patients with a reduction in the prostate-specific antigen (PSA) level by 50% or more (54% vs. 2%, P<0.001), the soft-tissue response rate (29% vs. 4%, P<0.001), the quality-of-life response rate (43% vs. 18%, P<0.001), the time to PSA progression (8.3 vs. 3.0 months; hazard ratio, 0.25; P<0.001), radiographic progression-free survival (8.3 vs. 2.9 months; hazard ratio, 0.40; P<0.001), and the time to the first skeletal-related event (16.7 vs. 13.3 months; hazard ratio, 0.69; P<0.001). Rates of fatigue, diarrhea, and hot flashes were higher in the enzalutamide group. Seizures were reported in five patients (0.6%) receiving enzalutamide.
Conclusions: Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy. (Funded by Medivation and Astellas Pharma Global Development; AFFIRM ClinicalTrials.gov number, NCT00974311.).
Source: PubMed