Development and Validation of a Prognostic Model for Overall Survival in Chemotherapy-Naïve Men with Metastatic Castration-Resistant Prostate Cancer
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. ClinicalTrials.gov: NCT01212991
Authors: Andrew J Armstrong, Division of Medical Oncology and Urology, Duke Cancer Institute, Duke University, Durham, NC, P Lin, Biostatistics (Lin) and Medical Affairs (Wong), Pfizer Inc., San Francisco, C S Higano, Medical Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, Cora N Sternberg, Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy, Guru Sonpavde, Division of Hematology and Oncology, the University of Alabama at Birmingham, Birmingham, AL, Bertrand Tombal, Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium, A J Templeton, Department of Oncology, St. Claraspital, and University of Basel, Basel, Switzerland, Karim Fizazi, MD, Ph.D., Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France, D Phung, Biostatistics, Astellas Pharma Europe B.V., Leiden, Netherlands, E K Wong, Biostatistics (Lin) and Medical Affairs (Wong), Pfizer Inc., San Francisco, CA, A Krivoshik, Medical Sciences, Astellas Pharma US, Inc., Northbrook, USA, T M Beer, Hematology/Medical Oncology, OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR
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