Enzalutamide in Metastatic Prostate Cancer before Chemotherapy

By T. Beer, A. Armstrong, D. Rathkopf, Y. Loriot, C. Sternberg, Celestia S. Higano, P. Iversen, S. Bhattacharya, J. Carles, S. Chowdhury and 18 more. New England Journal of Medicine, 2014

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BACKGROUND Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. METHODS In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival. RESULTS The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment. CONCLUSIONS Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.)

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/dcce03f532faed52e1efc5b9d1e81f366f3422d0

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Citations in the corpus

Enzalutamide in Men with Nonmetastatic, Castration‐Resistant Prostate Cancer (2018, neutral): “Decreased appetite 89 (10) 2 (<1) 18 (4) 1 (<1)”
A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). (2015, neutral): “84) Improved 3 [101]”
Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. (2016, background): “PCWG3 retains the PCWG2 criteria for PSA progression.(5,6,10,11) For nmCRPC, PCWG3 advises recording PSA doubling times (PSADTs) and focusing drug development efforts on patients with shorter times who have the greatest risk of developing detectable metastatic disease or symptoms, and dying of their”
Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer. (2017, background): “Although significant treatment advances have been made recently with the introduction of novel therapeutic agents, such as enzalutamide, abiraterone acetate, cabazitaxel, and radium 223, prognosis and long-term outcomes for patients with castration-resistant prostate cancer (CRPC) need to be improve”
EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. (2020, neutral): “A randomised phase III trial (PREVAIL) included a similar patient population and compared enzalutamide with placebo [110].”
Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy (2017, neutral): “of patients reporting treatment after progression) 535 535 535 535 Any Docetaxel Abiraterone Enzalutamide (441) (102) (38) (24) 70 374 434 448 (20) (51) (43) (52) 38 271 331 331 (7) (25) (18) (35) 23 145 162 165 (4) (12) (16) (15) 18”
Genetics and biology of prostate cancer (2018, background): “The potent AR antagonists enzalutamide and apalutamide can increase the survival of patients with mCRPC (Scher et al. 2012; Beer et al. 2014) and localized CRPC (Smith et al.”
EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. (2017, methodology): “A randomised phase 3 trial (PREVAIL) [76] included a similar patient population and compared enzalutamide and placebo.”
Integrative clinical genomics of advanced prostate cancer (2015, positive): “Genomic studies of metastatic prostate cancers demonstrated additional alterations in AR (Taplin et al., 1995) and in the androgen signaling pathway (Beltran et al., 2013; Grasso et al., 2012; Gundem et al., 2015; Hong et al., 2015), although these studies were performed predominantly using autopsy…”
Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study. (2018, neutral): “796 0 101 (50) 15 (56) 69 (52) 19 (45) 1 85 (42) 9 (33) 53 (40) 21 (50) 2 7 (3) 2 (7) 5 (4) 1 (2) Unknown 9 (4) 1 (4) 6 (5) 1 (2) Prior treatment First-generation antiandrogen (bicalutamide, flutamide, nilutamide) 182 (90) 25 (93) 118 (89) 38 (90) .”