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

Choung Soo Kim, Young Deuk Choi, Sang Eun Lee, Hyun Moo Lee, Takeshi Ueda, Junji Yonese, Takashi Fukagai, Edmund Chiong, Weber Lau, Sarang Abhyankar, Ad Theeuwes, Bertrand Tombal, Tomasz (Tom) Beer, Go Kimura

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    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- A nd 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- A nd 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.

    Original languageEnglish (US)
    Article numbere7223
    JournalMedicine (United States)
    Volume96
    Issue number27
    DOIs
    StatePublished - Jul 1 2017

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    Castration
    Prostatic Neoplasms
    Placebos
    Drug Therapy
    Prostate-Specific Antigen
    Disease-Free Survival
    Androgen Receptors
    MDV 3100
    Therapeutics
    Confidence Intervals
    Safety
    Survival
    Far East
    Population
    Androgens
    Pharmacokinetics
    Research Personnel

    Keywords

    • antineoplastic agents
    • Asia
    • castration-resistant
    • disease-free survival
    • MDV 3100
    • prostatic neoplasms

    ASJC Scopus subject areas

    • Medicine(all)

    Cite this

    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 (Tom); Kimura, Go.

    In: Medicine (United States), Vol. 96, No. 27, e7223, 01.07.2017.

    Research output: Contribution to journalArticle

    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 (Tom) ; 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. In: Medicine (United States). 2017 ; Vol. 96, No. 27.
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    title = "Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-na{\"i}ve, metastatic castration-resistant prostate cancer",
    abstract = "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-na{\"i}ve 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-na{\"i}ve 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- A nd 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- A nd 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.",
    keywords = "antineoplastic agents, Asia, castration-resistant, disease-free survival, MDV 3100, prostatic neoplasms",
    author = "Kim, {Choung Soo} and Choi, {Young Deuk} and Lee, {Sang Eun} and Lee, {Hyun Moo} and Takeshi Ueda and Junji Yonese and Takashi Fukagai and Edmund Chiong and Weber Lau and Sarang Abhyankar and Ad Theeuwes and Bertrand Tombal and Beer, {Tomasz (Tom)} and Go Kimura",
    year = "2017",
    month = "7",
    day = "1",
    doi = "10.1097/MD.0000000000007223",
    language = "English (US)",
    volume = "96",
    journal = "Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries",
    issn = "0025-7974",
    publisher = "Lippincott Williams and Wilkins",
    number = "27",

    }

    TY - JOUR

    T1 - 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

    AU - Kim, Choung Soo

    AU - Choi, Young Deuk

    AU - Lee, Sang Eun

    AU - Lee, Hyun Moo

    AU - Ueda, Takeshi

    AU - Yonese, Junji

    AU - Fukagai, Takashi

    AU - Chiong, Edmund

    AU - Lau, Weber

    AU - Abhyankar, Sarang

    AU - Theeuwes, Ad

    AU - Tombal, Bertrand

    AU - Beer, Tomasz (Tom)

    AU - Kimura, Go

    PY - 2017/7/1

    Y1 - 2017/7/1

    N2 - 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- A nd 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- A nd 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.

    AB - 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- A nd 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- A nd 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.

    KW - antineoplastic agents

    KW - Asia

    KW - castration-resistant

    KW - disease-free survival

    KW - MDV 3100

    KW - prostatic neoplasms

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    U2 - 10.1097/MD.0000000000007223

    DO - 10.1097/MD.0000000000007223

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    C2 - 28682871

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    JO - Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries

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