Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial

Joshi Alumkal, Simon Chowdhury, Yohann Loriot, Cora N. Sternberg, Johann S. de Bono, Bertrand Tombal, Joan Carles, Thomas W. Flaig, Tanya B. Dorff, De Phung, David Forer, Sarah B. Noonberg, Hank Mansbach, Tomasz (Tom) Beer, Celestia S. Higano

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Background: The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy. Patients and Methods: Prespecified analyses examined the coprimary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) only. All other efficacy analyses were post hoc. The visceral subgroup was divided into liver or lung subsets. Patients with both liver and lung metastases were included in the liver subset. Results: Of the 1717 patients in PREVAIL, 204 (12%) had visceral metastases at screening (liver only or liver/lung metastases, n = 74; lung only metastases, n = 130). In patients with liver metastases, enzalutamide was associated with an improvement in rPFS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.90) but not OS (HR, 1.04; 95% CI, 0.57-1.87). In patients with lung metastases only, the HR for rPFS (0.14; 95% CI, 0.06-0.36) and the HR for OS (0.59; 95% CI, 0.33-1.06) favored enzalutamide over placebo. Patients with liver metastases had worse outcomes than those with lung metastases, regardless of treatment. Enzalutamide was well tolerated in patients with visceral disease. Conclusions: Enzalutamide is an active first-line treatment option for men with asymptomatic or mildly symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer and visceral disease. Patients with lung-only disease fared better than patients with liver disease, regardless of treatment.

    Original languageEnglish (US)
    JournalClinical Genitourinary Cancer
    DOIs
    StateAccepted/In press - Dec 14 2016

    Fingerprint

    Castration
    Prostatic Neoplasms
    Neoplasm Metastasis
    Liver
    Lung
    Confidence Intervals
    Disease-Free Survival
    Drug Therapy
    Survival
    MDV 3100
    Placebos
    Therapeutics
    Androgens
    Lung Diseases
    Liver Diseases

    Keywords

    • Androgen receptor inhibitor
    • Chemotherapy-naive
    • Metastases
    • Phase III
    • Survival analysis

    ASJC Scopus subject areas

    • Oncology
    • Urology

    Cite this

    Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial. / Alumkal, Joshi; Chowdhury, Simon; Loriot, Yohann; Sternberg, Cora N.; de Bono, Johann S.; Tombal, Bertrand; Carles, Joan; Flaig, Thomas W.; Dorff, Tanya B.; Phung, De; Forer, David; Noonberg, Sarah B.; Mansbach, Hank; Beer, Tomasz (Tom); Higano, Celestia S.

    In: Clinical Genitourinary Cancer, 14.12.2016.

    Research output: Contribution to journalArticle

    Alumkal, J, Chowdhury, S, Loriot, Y, Sternberg, CN, de Bono, JS, Tombal, B, Carles, J, Flaig, TW, Dorff, TB, Phung, D, Forer, D, Noonberg, SB, Mansbach, H, Beer, TT & Higano, CS 2016, 'Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial', Clinical Genitourinary Cancer. https://doi.org/10.1016/j.clgc.2017.02.007
    Alumkal, Joshi ; Chowdhury, Simon ; Loriot, Yohann ; Sternberg, Cora N. ; de Bono, Johann S. ; Tombal, Bertrand ; Carles, Joan ; Flaig, Thomas W. ; Dorff, Tanya B. ; Phung, De ; Forer, David ; Noonberg, Sarah B. ; Mansbach, Hank ; Beer, Tomasz (Tom) ; Higano, Celestia S. / Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial. In: Clinical Genitourinary Cancer. 2016.
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    title = "Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial",
    abstract = "Background: The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy. Patients and Methods: Prespecified analyses examined the coprimary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) only. All other efficacy analyses were post hoc. The visceral subgroup was divided into liver or lung subsets. Patients with both liver and lung metastases were included in the liver subset. Results: Of the 1717 patients in PREVAIL, 204 (12{\%}) had visceral metastases at screening (liver only or liver/lung metastases, n = 74; lung only metastases, n = 130). In patients with liver metastases, enzalutamide was associated with an improvement in rPFS (hazard ratio [HR], 0.44; 95{\%} confidence interval [CI], 0.22-0.90) but not OS (HR, 1.04; 95{\%} CI, 0.57-1.87). In patients with lung metastases only, the HR for rPFS (0.14; 95{\%} CI, 0.06-0.36) and the HR for OS (0.59; 95{\%} CI, 0.33-1.06) favored enzalutamide over placebo. Patients with liver metastases had worse outcomes than those with lung metastases, regardless of treatment. Enzalutamide was well tolerated in patients with visceral disease. Conclusions: Enzalutamide is an active first-line treatment option for men with asymptomatic or mildly symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer and visceral disease. Patients with lung-only disease fared better than patients with liver disease, regardless of treatment.",
    keywords = "Androgen receptor inhibitor, Chemotherapy-naive, Metastases, Phase III, Survival analysis",
    author = "Joshi Alumkal and Simon Chowdhury and Yohann Loriot and Sternberg, {Cora N.} and {de Bono}, {Johann S.} and Bertrand Tombal and Joan Carles and Flaig, {Thomas W.} and Dorff, {Tanya B.} and De Phung and David Forer and Noonberg, {Sarah B.} and Hank Mansbach and Beer, {Tomasz (Tom)} and Higano, {Celestia S.}",
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    month = "12",
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    TY - JOUR

    T1 - Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial

    AU - Alumkal, Joshi

    AU - Chowdhury, Simon

    AU - Loriot, Yohann

    AU - Sternberg, Cora N.

    AU - de Bono, Johann S.

    AU - Tombal, Bertrand

    AU - Carles, Joan

    AU - Flaig, Thomas W.

    AU - Dorff, Tanya B.

    AU - Phung, De

    AU - Forer, David

    AU - Noonberg, Sarah B.

    AU - Mansbach, Hank

    AU - Beer, Tomasz (Tom)

    AU - Higano, Celestia S.

    PY - 2016/12/14

    Y1 - 2016/12/14

    N2 - Background: The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy. Patients and Methods: Prespecified analyses examined the coprimary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) only. All other efficacy analyses were post hoc. The visceral subgroup was divided into liver or lung subsets. Patients with both liver and lung metastases were included in the liver subset. Results: Of the 1717 patients in PREVAIL, 204 (12%) had visceral metastases at screening (liver only or liver/lung metastases, n = 74; lung only metastases, n = 130). In patients with liver metastases, enzalutamide was associated with an improvement in rPFS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.90) but not OS (HR, 1.04; 95% CI, 0.57-1.87). In patients with lung metastases only, the HR for rPFS (0.14; 95% CI, 0.06-0.36) and the HR for OS (0.59; 95% CI, 0.33-1.06) favored enzalutamide over placebo. Patients with liver metastases had worse outcomes than those with lung metastases, regardless of treatment. Enzalutamide was well tolerated in patients with visceral disease. Conclusions: Enzalutamide is an active first-line treatment option for men with asymptomatic or mildly symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer and visceral disease. Patients with lung-only disease fared better than patients with liver disease, regardless of treatment.

    AB - Background: The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy. Patients and Methods: Prespecified analyses examined the coprimary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) only. All other efficacy analyses were post hoc. The visceral subgroup was divided into liver or lung subsets. Patients with both liver and lung metastases were included in the liver subset. Results: Of the 1717 patients in PREVAIL, 204 (12%) had visceral metastases at screening (liver only or liver/lung metastases, n = 74; lung only metastases, n = 130). In patients with liver metastases, enzalutamide was associated with an improvement in rPFS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.90) but not OS (HR, 1.04; 95% CI, 0.57-1.87). In patients with lung metastases only, the HR for rPFS (0.14; 95% CI, 0.06-0.36) and the HR for OS (0.59; 95% CI, 0.33-1.06) favored enzalutamide over placebo. Patients with liver metastases had worse outcomes than those with lung metastases, regardless of treatment. Enzalutamide was well tolerated in patients with visceral disease. Conclusions: Enzalutamide is an active first-line treatment option for men with asymptomatic or mildly symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer and visceral disease. Patients with lung-only disease fared better than patients with liver disease, regardless of treatment.

    KW - Androgen receptor inhibitor

    KW - Chemotherapy-naive

    KW - Metastases

    KW - Phase III

    KW - Survival analysis

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