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Updated: Mar 19, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Modeling the Relationship Between Exposure to Abiraterone and Prostate-Specific Antigen Dynamics in Patients with
Xu Steven Xu1, Charles J Ryan2, Kim Stuyckens3
1Janssen Research & Development, 920 Route 202, Raritan, NJ, 08869, USA. sxu26@its.jnj.com.
Background And Objectives:
Recent analysis revealed strong associations between prostate-specific antigen (PSA) dynamics and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) and supported PSA dynamics as bridging surrogacy endpoints for clinical benefit from treatment with abiraterone acetate plus prednisone. This analysis aimed to investigate the abiraterone exposure-PSA dynamics relationship in mCRPC.
Methods:
Abiraterone pharmacokinetics-PSA models were constructed using data from the COU-AA-301 (chemotherapy-pretreated) and COU-AA-302 (chemotherapy-naïve) trials comparing abiraterone acetate 1000 mg/day plus prednisone 5 mg twice daily with prednisone alone in mCRPC. The drug effect-PSA dynamics relationship was modeled as a function of selected pharmacokinetic measures. The influences of baseline demographic variables, laboratory values, and disease status on PSA dynamics were assessed.
Results:
A tumor growth inhibition model best described PSA dynamics post-treatment with abiraterone acetate. Abiraterone acetate treatment in chemotherapy-pretreated and chemotherapy-naïve patients increased the PSA decay rate (k dec) to the same extent (1.28-fold, 95 % confidence interval [CI] 0.58-1.98; and 0.93-fold, 95 % CI 0.6-1.27, respectively). Lower baseline lactate dehydrogenase and higher baseline testosterone significantly increased k dec. Findings from our analysis suggest a maximum-effect relationship between abiraterone trough concentration and PSA dynamics in both patient populations. The majority of patients had a steady-state trough concentration greater than the estimated half maximal effective concentration.
Conclusion:
The model appropriately described the exposure-response relationship between abiraterone and PSA dynamics in chemotherapy-pretreated and chemotherapy-naïve patients following oral administration of abiraterone acetate.
