Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.
Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.
Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.
They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.
Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.
The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.
The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.
Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.
“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.
The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.
“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.
The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).
SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.