External Validation of a Prognostic Model for Overall Survival (OS) in Men with Metastatic Castration-resistant Prostate Cancer (mCRPC)

Background: We have previously developed and externally validated a prognostic model of OS in men with mCRPC treated with docetaxel (D), which included eight predictors: opioid analgesic use, ECOG performance status, albumin, disease site, LDH, hemoglobin, PSA, and alkaline phosphatase. We have used this model to develop prognostic risk groups. We sought to externally validate this model in a broader group of men with mCRPC and in specific subgroups (White, Black, Asian patients, different age groups) and to validate the two and three prognostic risk groups in this large dataset.

Methods: Data from 5,790 mCRPC men randomized on 5 phase III trials were utilized to validate the prognostic model of OS: D +/- zibotentan (ENTHUSE), D +/- lenalidomide (MAINSAIL), D +/- dasatinib (READY), D+/- custirsen (SYNERGY), and tasquinimod/placebo)). We applied the estimated parameters from the prognostic model to each of the five data sets and computed a risk score. We assessed the predictive performance of the model by computing the time-dependent area under the receiver operating characteristic curve (tAUC) and validated the two-risk (low, high) and three-risk prognostic risk groups (low, intermediate, high) that were defined by the model. Results: The tAUC for the different groups is presented in the table. Race, age, and treatment subsets had similar results. For the two prognostic risk groups, the median OS in the low and high groups were 27.6 months (95% CI = 26.6-28.7) and 13.8 months (95% CI = 13.3-14.4). For the three prognostic risk group, median OS in the low, intermediate and high groups were 29.7 months (95% CI = 28.3-31.4), 19.0 month (95% CI = 18.3-20.4) and 12.1 months (95% CI = 11.5-12.9), respectively.

Conclusions: This prognostic model for OS in men with mCRPC has been validated in a larger dataset, yields similar results across race, age and treatment groups. The model is robust and can be used to identify prognostic risk groups of patients for stratification and enrichment trials. Clinical trial information: NCT00626548.

Authors: Susan Halabi, Sandipan Dutta, John C. Araujo, Christopher Logothetis, Cora N. Sternberg, Andrew J. Armstrong, Michael Anthony Carducci, Kim N. Chi, Johann S. De Bono, Daniel Peter Petrylak, Karim Fizazi, Celestia S. Higano, Eric Jay Small, William Kevin Kelly
Duke University Medical Center, Durham, NC; Duke University, Durham, NC; The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; Weill Cornell Medicine, New York, NY; Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC; Sidney Kimmel Cancer Center At Johns Hopkins, Baltimore, MD; BC Cancer, Vancouver, BC, Canada; Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom; Yale School of Medicine, New Haven, CT; Institut Gustave Roussy, University of Paris-Sud, Villejuif, France; University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA

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