Development and validation of a prognostic model for overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer

A. J. Armstrong, P. Lin, C. S. Higano, C. N. Sternberg, G. Sonpavde, B. Tombal, A. J. Templeton, K. Fizazi, D. Phung, E. K. Wong, A. Krivoshik, Tomasz (Tom) Beer

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    Background: Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for overall survival (OS) in chemotherapy-naïve men with mCRPC treated with enzalutamide. Patients and methods: Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2 : 1 into training (n = 1159) and testing (n = 550) sets. Using the training set, 23 predefined variables were analyzed and a multivariable model predicting OS was developed and validated in an independent testing set. Results: Patient characteristics and outcomes were well balanced between training and testing sets; median OS was 32.7 months in each. The final validated multivariable model included 11 independent prognostic variables. Median OS for low-, intermediate-, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached (NYR) (95% CI NYR-NYR), 34.2 months (31.5-NYR), and 21.1 months (17.5-25.0), respectively. Hazard ratios (95% CI) for OS in the low- and intermediate-risk groups versus high-risk group were 0.20 (0.14-0.29) and 0.40 (0.30-0.53), respectively. Secondary outcomes of response and progression differed widely in model-defined risk groups. Enzalutamide improved outcomes in all prognostic risk groups. Conclusions: Our validated prognostic model incorporates variables routinely collected in chemotherapy-naïve men with mCRPC treated with enzalutamide, identifying subsets of patients with widely differing survival outcomes that provide useful information for external validation, patient care, and clinical trial design. Trial registration: ClinicalTrials.gov: NCT01212991.

    Original languageEnglish (US)
    Pages (from-to)2200-2207
    Number of pages8
    JournalAnnals of oncology : official journal of the European Society for Medical Oncology
    Volume29
    Issue number11
    DOIs
    StatePublished - Nov 1 2018

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    Castration
    Prostatic Neoplasms
    Drug Therapy
    Survival
    Patient Care
    Placebos
    Clinical Trials
    Databases
    MDV 3100

    ASJC Scopus subject areas

    • Hematology
    • Oncology

    Cite this

    Development and validation of a prognostic model for overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer. / Armstrong, A. J.; Lin, P.; Higano, C. S.; Sternberg, C. N.; Sonpavde, G.; Tombal, B.; Templeton, A. J.; Fizazi, K.; Phung, D.; Wong, E. K.; Krivoshik, A.; Beer, Tomasz (Tom).

    In: Annals of oncology : official journal of the European Society for Medical Oncology, Vol. 29, No. 11, 01.11.2018, p. 2200-2207.

    Research output: Contribution to journalArticle

    Armstrong, A. J. ; Lin, P. ; Higano, C. S. ; Sternberg, C. N. ; Sonpavde, G. ; Tombal, B. ; Templeton, A. J. ; Fizazi, K. ; Phung, D. ; Wong, E. K. ; Krivoshik, A. ; Beer, Tomasz (Tom). / Development and validation of a prognostic model for overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer. In: Annals of oncology : official journal of the European Society for Medical Oncology. 2018 ; Vol. 29, No. 11. pp. 2200-2207.
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    title = "Development and validation of a prognostic model for overall survival in chemotherapy-na{\"i}ve men with metastatic castration-resistant prostate cancer",
    abstract = "Background: Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for overall survival (OS) in chemotherapy-na{\"i}ve men with mCRPC treated with enzalutamide. Patients and methods: Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2 : 1 into training (n = 1159) and testing (n = 550) sets. Using the training set, 23 predefined variables were analyzed and a multivariable model predicting OS was developed and validated in an independent testing set. Results: Patient characteristics and outcomes were well balanced between training and testing sets; median OS was 32.7 months in each. The final validated multivariable model included 11 independent prognostic variables. Median OS for low-, intermediate-, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached (NYR) (95{\%} CI NYR-NYR), 34.2 months (31.5-NYR), and 21.1 months (17.5-25.0), respectively. Hazard ratios (95{\%} CI) for OS in the low- and intermediate-risk groups versus high-risk group were 0.20 (0.14-0.29) and 0.40 (0.30-0.53), respectively. Secondary outcomes of response and progression differed widely in model-defined risk groups. Enzalutamide improved outcomes in all prognostic risk groups. Conclusions: Our validated prognostic model incorporates variables routinely collected in chemotherapy-na{\"i}ve men with mCRPC treated with enzalutamide, identifying subsets of patients with widely differing survival outcomes that provide useful information for external validation, patient care, and clinical trial design. Trial registration: ClinicalTrials.gov: NCT01212991.",
    author = "Armstrong, {A. J.} and P. Lin and Higano, {C. S.} and Sternberg, {C. N.} and G. Sonpavde and B. Tombal and Templeton, {A. J.} and K. Fizazi and D. Phung and Wong, {E. K.} and A. Krivoshik and Beer, {Tomasz (Tom)}",
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    T1 - Development and validation of a prognostic model for overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer

    AU - Armstrong, A. J.

    AU - Lin, P.

    AU - Higano, C. S.

    AU - Sternberg, C. N.

    AU - Sonpavde, G.

    AU - Tombal, B.

    AU - Templeton, A. J.

    AU - Fizazi, K.

    AU - Phung, D.

    AU - Wong, E. K.

    AU - Krivoshik, A.

    AU - Beer, Tomasz (Tom)

    PY - 2018/11/1

    Y1 - 2018/11/1

    N2 - Background: Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for overall survival (OS) in chemotherapy-naïve men with mCRPC treated with enzalutamide. Patients and methods: Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2 : 1 into training (n = 1159) and testing (n = 550) sets. Using the training set, 23 predefined variables were analyzed and a multivariable model predicting OS was developed and validated in an independent testing set. Results: Patient characteristics and outcomes were well balanced between training and testing sets; median OS was 32.7 months in each. The final validated multivariable model included 11 independent prognostic variables. Median OS for low-, intermediate-, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached (NYR) (95% CI NYR-NYR), 34.2 months (31.5-NYR), and 21.1 months (17.5-25.0), respectively. Hazard ratios (95% CI) for OS in the low- and intermediate-risk groups versus high-risk group were 0.20 (0.14-0.29) and 0.40 (0.30-0.53), respectively. Secondary outcomes of response and progression differed widely in model-defined risk groups. Enzalutamide improved outcomes in all prognostic risk groups. Conclusions: Our validated prognostic model incorporates variables routinely collected in chemotherapy-naïve men with mCRPC treated with enzalutamide, identifying subsets of patients with widely differing survival outcomes that provide useful information for external validation, patient care, and clinical trial design. Trial registration: ClinicalTrials.gov: NCT01212991.

    AB - Background: Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for overall survival (OS) in chemotherapy-naïve men with mCRPC treated with enzalutamide. Patients and methods: Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2 : 1 into training (n = 1159) and testing (n = 550) sets. Using the training set, 23 predefined variables were analyzed and a multivariable model predicting OS was developed and validated in an independent testing set. Results: Patient characteristics and outcomes were well balanced between training and testing sets; median OS was 32.7 months in each. The final validated multivariable model included 11 independent prognostic variables. Median OS for low-, intermediate-, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached (NYR) (95% CI NYR-NYR), 34.2 months (31.5-NYR), and 21.1 months (17.5-25.0), respectively. Hazard ratios (95% CI) for OS in the low- and intermediate-risk groups versus high-risk group were 0.20 (0.14-0.29) and 0.40 (0.30-0.53), respectively. Secondary outcomes of response and progression differed widely in model-defined risk groups. Enzalutamide improved outcomes in all prognostic risk groups. Conclusions: Our validated prognostic model incorporates variables routinely collected in chemotherapy-naïve men with mCRPC treated with enzalutamide, identifying subsets of patients with widely differing survival outcomes that provide useful information for external validation, patient care, and clinical trial design. Trial registration: ClinicalTrials.gov: NCT01212991.

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