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Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer

BACKGROUND: Enzalutamide is an androgen receptor (AR) inhibitor that acts on different steps in the AR signaling pathway. In PREVAIL, an international, phase III, double-blind, placebo-controlled trial, enzalutamide significantly reduced the risk of radiographic progression by 81% (hazard ratio [HR]...

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Autores principales: Kim, Choung Soo, Choi, Young Deuk, Lee, Sang Eun, Lee, Hyun Moo, Ueda, Takeshi, Yonese, Junji, Fukagai, Takashi, Chiong, Edmund, Lau, Weber, Abhyankar, Sarang, Theeuwes, Ad, Tombal, Bertrand, Beer, Tomasz M., Kimura, Go
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502144/
https://www.ncbi.nlm.nih.gov/pubmed/28682871
http://dx.doi.org/10.1097/MD.0000000000007223
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author Kim, Choung Soo
Choi, Young Deuk
Lee, Sang Eun
Lee, Hyun Moo
Ueda, Takeshi
Yonese, Junji
Fukagai, Takashi
Chiong, Edmund
Lau, Weber
Abhyankar, Sarang
Theeuwes, Ad
Tombal, Bertrand
Beer, Tomasz M.
Kimura, Go
author_facet Kim, Choung Soo
Choi, Young Deuk
Lee, Sang Eun
Lee, Hyun Moo
Ueda, Takeshi
Yonese, Junji
Fukagai, Takashi
Chiong, Edmund
Lau, Weber
Abhyankar, Sarang
Theeuwes, Ad
Tombal, Bertrand
Beer, Tomasz M.
Kimura, Go
author_sort Kim, Choung Soo
collection PubMed
description BACKGROUND: Enzalutamide is an androgen receptor (AR) inhibitor that acts on different steps in the AR signaling pathway. In PREVAIL, an international, phase III, double-blind, placebo-controlled trial, enzalutamide significantly reduced the risk of radiographic progression by 81% (hazard ratio [HR], 0.19; P < .0001) and reduced the risk of death by 29% (HR, 0.71; P < .0001) compared with placebo in chemotherapy-naïve men with metastatic castration-resistant prostate cancer. METHODS: To evaluate treatment effects, safety, and pharmacokinetics of enzalutamide in East Asian patients from the PREVAIL trial, we performed a post hoc analysis of the Japanese, Korean, and Singaporean patients. PREVAIL enrolled patients with asymptomatic or mildly symptomatic chemotherapy-naïve metastatic castration-resistant prostate cancer who had progressed on androgen deprivation therapy. During the study, patients received enzalutamide (160 mg/d) or placebo (1:1) until death or discontinuation because of radiographic progression or skeletal-related event and initiation of subsequent therapy. Centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS) were coprimary endpoints. The secondary endpoints of the PREVAIL trial were investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression, and PSA response (≥50% decline). RESULTS: Of 1717 patients, 148 patients were enrolled at sites in East Asia (enzalutamide 73, placebo 75). Treatment effect of enzalutamide versus placebo was consistent with that for the overall population as indicated by the HRs (95% confidence interval) of 0.38 (0.10–1.44) for centrally assessed rPFS, 0.59 (0.29–1.23) for OS, 0.33 (0.19–0.60) for time to chemotherapy, and 0.32 (0.20–0.50) for time to PSA progression. In East Asian patients, PSA responses were observed in 68.5% and 14.7% of enzalutamide- and placebo-treated patients, respectively. The enzalutamide plasma concentration ratio (East Asian:non-Asian patients) was 1.12 (90% confidence interval, 1.05–1.20) at 13 weeks. Treatment-related adverse events grade ≥ 3 occurred in 1.4% and 2.7% of enzalutamide- and placebo-treated East Asian patients, respectively. CONCLUSIONS: Treatment effects and safety of enzalutamide in East Asian patients were generally consistent with those observed in the overall study population from PREVAIL. CLINICALTRIALS.GOV NUMBER: NCT01212991
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spelling pubmed-55021442017-07-18 Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer Kim, Choung Soo Choi, Young Deuk Lee, Sang Eun Lee, Hyun Moo Ueda, Takeshi Yonese, Junji Fukagai, Takashi Chiong, Edmund Lau, Weber Abhyankar, Sarang Theeuwes, Ad Tombal, Bertrand Beer, Tomasz M. Kimura, Go Medicine (Baltimore) 7300 BACKGROUND: Enzalutamide is an androgen receptor (AR) inhibitor that acts on different steps in the AR signaling pathway. In PREVAIL, an international, phase III, double-blind, placebo-controlled trial, enzalutamide significantly reduced the risk of radiographic progression by 81% (hazard ratio [HR], 0.19; P < .0001) and reduced the risk of death by 29% (HR, 0.71; P < .0001) compared with placebo in chemotherapy-naïve men with metastatic castration-resistant prostate cancer. METHODS: To evaluate treatment effects, safety, and pharmacokinetics of enzalutamide in East Asian patients from the PREVAIL trial, we performed a post hoc analysis of the Japanese, Korean, and Singaporean patients. PREVAIL enrolled patients with asymptomatic or mildly symptomatic chemotherapy-naïve metastatic castration-resistant prostate cancer who had progressed on androgen deprivation therapy. During the study, patients received enzalutamide (160 mg/d) or placebo (1:1) until death or discontinuation because of radiographic progression or skeletal-related event and initiation of subsequent therapy. Centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS) were coprimary endpoints. The secondary endpoints of the PREVAIL trial were investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression, and PSA response (≥50% decline). RESULTS: Of 1717 patients, 148 patients were enrolled at sites in East Asia (enzalutamide 73, placebo 75). Treatment effect of enzalutamide versus placebo was consistent with that for the overall population as indicated by the HRs (95% confidence interval) of 0.38 (0.10–1.44) for centrally assessed rPFS, 0.59 (0.29–1.23) for OS, 0.33 (0.19–0.60) for time to chemotherapy, and 0.32 (0.20–0.50) for time to PSA progression. In East Asian patients, PSA responses were observed in 68.5% and 14.7% of enzalutamide- and placebo-treated patients, respectively. The enzalutamide plasma concentration ratio (East Asian:non-Asian patients) was 1.12 (90% confidence interval, 1.05–1.20) at 13 weeks. Treatment-related adverse events grade ≥ 3 occurred in 1.4% and 2.7% of enzalutamide- and placebo-treated East Asian patients, respectively. CONCLUSIONS: Treatment effects and safety of enzalutamide in East Asian patients were generally consistent with those observed in the overall study population from PREVAIL. CLINICALTRIALS.GOV NUMBER: NCT01212991 Wolters Kluwer Health 2017-07-07 /pmc/articles/PMC5502144/ /pubmed/28682871 http://dx.doi.org/10.1097/MD.0000000000007223 Text en Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0
spellingShingle 7300
Kim, Choung Soo
Choi, Young Deuk
Lee, Sang Eun
Lee, Hyun Moo
Ueda, Takeshi
Yonese, Junji
Fukagai, Takashi
Chiong, Edmund
Lau, Weber
Abhyankar, Sarang
Theeuwes, Ad
Tombal, Bertrand
Beer, Tomasz M.
Kimura, Go
Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer
title Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer
title_full Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer
title_fullStr Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer
title_full_unstemmed Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer
title_short Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer
title_sort post hoc analyses of east asian patients from the randomized placebo-controlled prevail trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer
topic 7300
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5502144/
https://www.ncbi.nlm.nih.gov/pubmed/28682871
http://dx.doi.org/10.1097/MD.0000000000007223
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