Clinical Outcomes of Chemotherapy Naïve Men with Metastatic Castration Resistant Prostate Cancer and Low Baseline Prostate Specific Antigen Treated with Enzalutamide vs Placebo

Mary Ellen Taplin, Andrew J. Armstrong, Ping Lin, Andrew Krivoshik, De Phung, Teresa Parli, Bertrand Tombal, Tomasz (Tom) Beer

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    Purpose: Metastatic castration resistant prostate cancer with low baseline prostate specific antigen represents an early stage in the natural history of castration resistant prostate cancer progression (low volume disease), low prostate specific antigen producing disease or disease that is less dependent on androgen receptor biology (high volume disease). We analyzed outcomes in men with low prostate specific antigen and a high disease burden who received the oral androgen receptor inhibitor enzalutamide in the PREVAIL (Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients with Progressive Metastatic Prostate Cancer) study. Materials and Methods: In this exploratory analysis low baseline prostate specific antigen was defined as less than 10 ng/ml. Post hoc analyses included radiographic progression-free and overall survival in the once daily enzalutamide and placebo arms. Patients were stratified post hoc by high volume disease, defined as more than 4 bone metastases and/or visceral disease, and low volume disease, defined as 4 or fewer bone metastases with no visceral disease. Results: Of 1,717 patients enrolled in PREVAIL 242 (14.1%) had low baseline prostate specific antigen, including 110 with high volume disease. Enzalutamide decreased the risk of radiographic progression relative to placebo in patients with low baseline prostate specific antigen (HR 0.20, 95% CI 0.10-0.42). This decrease was irrespective of tumor burden (high volume disease HR 0.17, 95% CI 0.06-0.51 and low volume disease HR 0.25, 95% CI 0.09-0.70). Median overall survival was not reached in patients with low baseline prostate specific antigen in either treatment arm. Conclusions: Chemotherapy naïve men with metastatic castration resistant prostate cancer and low baseline prostate specific antigen irrespective of disease burden may benefit from enzalutamide. This indicates that targeting the androgen receptor signaling pathway is a therapeutic option in similar patients.

    Original languageEnglish (US)
    JournalJournal of Urology
    DOIs
    StateAccepted/In press - 2017

    Fingerprint

    Castration
    Prostate-Specific Antigen
    Prostatic Neoplasms
    Placebos
    Drug Therapy
    Androgen Receptors
    MDV 3100
    Neoplasm Metastasis
    Bone and Bones
    Tumor Burden
    Natural History
    Disease-Free Survival

    Keywords

    • Androgen
    • Castration-resistant
    • MDV 3100
    • Prostate-specific antigen
    • Prostatic neoplasms
    • Receptors
    • Treatment outcome

    ASJC Scopus subject areas

    • Urology

    Cite this

    Clinical Outcomes of Chemotherapy Naïve Men with Metastatic Castration Resistant Prostate Cancer and Low Baseline Prostate Specific Antigen Treated with Enzalutamide vs Placebo. / Taplin, Mary Ellen; Armstrong, Andrew J.; Lin, Ping; Krivoshik, Andrew; Phung, De; Parli, Teresa; Tombal, Bertrand; Beer, Tomasz (Tom).

    In: Journal of Urology, 2017.

    Research output: Contribution to journalArticle

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    title = "Clinical Outcomes of Chemotherapy Na{\"i}ve Men with Metastatic Castration Resistant Prostate Cancer and Low Baseline Prostate Specific Antigen Treated with Enzalutamide vs Placebo",
    abstract = "Purpose: Metastatic castration resistant prostate cancer with low baseline prostate specific antigen represents an early stage in the natural history of castration resistant prostate cancer progression (low volume disease), low prostate specific antigen producing disease or disease that is less dependent on androgen receptor biology (high volume disease). We analyzed outcomes in men with low prostate specific antigen and a high disease burden who received the oral androgen receptor inhibitor enzalutamide in the PREVAIL (Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients with Progressive Metastatic Prostate Cancer) study. Materials and Methods: In this exploratory analysis low baseline prostate specific antigen was defined as less than 10 ng/ml. Post hoc analyses included radiographic progression-free and overall survival in the once daily enzalutamide and placebo arms. Patients were stratified post hoc by high volume disease, defined as more than 4 bone metastases and/or visceral disease, and low volume disease, defined as 4 or fewer bone metastases with no visceral disease. Results: Of 1,717 patients enrolled in PREVAIL 242 (14.1{\%}) had low baseline prostate specific antigen, including 110 with high volume disease. Enzalutamide decreased the risk of radiographic progression relative to placebo in patients with low baseline prostate specific antigen (HR 0.20, 95{\%} CI 0.10-0.42). This decrease was irrespective of tumor burden (high volume disease HR 0.17, 95{\%} CI 0.06-0.51 and low volume disease HR 0.25, 95{\%} CI 0.09-0.70). Median overall survival was not reached in patients with low baseline prostate specific antigen in either treatment arm. Conclusions: Chemotherapy na{\"i}ve men with metastatic castration resistant prostate cancer and low baseline prostate specific antigen irrespective of disease burden may benefit from enzalutamide. This indicates that targeting the androgen receptor signaling pathway is a therapeutic option in similar patients.",
    keywords = "Androgen, Castration-resistant, MDV 3100, Prostate-specific antigen, Prostatic neoplasms, Receptors, Treatment outcome",
    author = "Taplin, {Mary Ellen} and Armstrong, {Andrew J.} and Ping Lin and Andrew Krivoshik and De Phung and Teresa Parli and Bertrand Tombal and Beer, {Tomasz (Tom)}",
    year = "2017",
    doi = "10.1016/j.juro.2017.07.071",
    language = "English (US)",
    journal = "Journal of Urology",
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    T1 - Clinical Outcomes of Chemotherapy Naïve Men with Metastatic Castration Resistant Prostate Cancer and Low Baseline Prostate Specific Antigen Treated with Enzalutamide vs Placebo

    AU - Taplin, Mary Ellen

    AU - Armstrong, Andrew J.

    AU - Lin, Ping

    AU - Krivoshik, Andrew

    AU - Phung, De

    AU - Parli, Teresa

    AU - Tombal, Bertrand

    AU - Beer, Tomasz (Tom)

    PY - 2017

    Y1 - 2017

    N2 - Purpose: Metastatic castration resistant prostate cancer with low baseline prostate specific antigen represents an early stage in the natural history of castration resistant prostate cancer progression (low volume disease), low prostate specific antigen producing disease or disease that is less dependent on androgen receptor biology (high volume disease). We analyzed outcomes in men with low prostate specific antigen and a high disease burden who received the oral androgen receptor inhibitor enzalutamide in the PREVAIL (Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients with Progressive Metastatic Prostate Cancer) study. Materials and Methods: In this exploratory analysis low baseline prostate specific antigen was defined as less than 10 ng/ml. Post hoc analyses included radiographic progression-free and overall survival in the once daily enzalutamide and placebo arms. Patients were stratified post hoc by high volume disease, defined as more than 4 bone metastases and/or visceral disease, and low volume disease, defined as 4 or fewer bone metastases with no visceral disease. Results: Of 1,717 patients enrolled in PREVAIL 242 (14.1%) had low baseline prostate specific antigen, including 110 with high volume disease. Enzalutamide decreased the risk of radiographic progression relative to placebo in patients with low baseline prostate specific antigen (HR 0.20, 95% CI 0.10-0.42). This decrease was irrespective of tumor burden (high volume disease HR 0.17, 95% CI 0.06-0.51 and low volume disease HR 0.25, 95% CI 0.09-0.70). Median overall survival was not reached in patients with low baseline prostate specific antigen in either treatment arm. Conclusions: Chemotherapy naïve men with metastatic castration resistant prostate cancer and low baseline prostate specific antigen irrespective of disease burden may benefit from enzalutamide. This indicates that targeting the androgen receptor signaling pathway is a therapeutic option in similar patients.

    AB - Purpose: Metastatic castration resistant prostate cancer with low baseline prostate specific antigen represents an early stage in the natural history of castration resistant prostate cancer progression (low volume disease), low prostate specific antigen producing disease or disease that is less dependent on androgen receptor biology (high volume disease). We analyzed outcomes in men with low prostate specific antigen and a high disease burden who received the oral androgen receptor inhibitor enzalutamide in the PREVAIL (Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients with Progressive Metastatic Prostate Cancer) study. Materials and Methods: In this exploratory analysis low baseline prostate specific antigen was defined as less than 10 ng/ml. Post hoc analyses included radiographic progression-free and overall survival in the once daily enzalutamide and placebo arms. Patients were stratified post hoc by high volume disease, defined as more than 4 bone metastases and/or visceral disease, and low volume disease, defined as 4 or fewer bone metastases with no visceral disease. Results: Of 1,717 patients enrolled in PREVAIL 242 (14.1%) had low baseline prostate specific antigen, including 110 with high volume disease. Enzalutamide decreased the risk of radiographic progression relative to placebo in patients with low baseline prostate specific antigen (HR 0.20, 95% CI 0.10-0.42). This decrease was irrespective of tumor burden (high volume disease HR 0.17, 95% CI 0.06-0.51 and low volume disease HR 0.25, 95% CI 0.09-0.70). Median overall survival was not reached in patients with low baseline prostate specific antigen in either treatment arm. Conclusions: Chemotherapy naïve men with metastatic castration resistant prostate cancer and low baseline prostate specific antigen irrespective of disease burden may benefit from enzalutamide. This indicates that targeting the androgen receptor signaling pathway is a therapeutic option in similar patients.

    KW - Androgen

    KW - Castration-resistant

    KW - MDV 3100

    KW - Prostate-specific antigen

    KW - Prostatic neoplasms

    KW - Receptors

    KW - Treatment outcome

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