Exposure–response analyses of abiraterone and its metabolites in real-world patients with metastatic castration-resistant prostate cancer

M. van Nuland, S. L. Groenland, A. M. Bergman, N. Steeghs, H. Rosing, N. Venekamp, A. D.R. Huitema, J. H. Beijnen

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Background: Abiraterone acetate is an oral 17α-hydroxylase/C17,20-lyase (CYP17) inhibitor approved for the treatment of metastatic castration-resistant prostate cancer (mCPRC) patients. Previously, a prospective observational trial demonstrated a relationship between abiraterone trough concentrations (Cmin) in plasma and treatment efficacy. The aim of our study was to investigate the exposure–response relationship of abiraterone and its metabolites, and to study if the proposed target for abiraterone of 8.4 ng/mL is feasible in a “real-world” patient cohort. Patients and methods: mCRPC patients who had at least one abiraterone plasma concentration at steady-state were included in this study. Plasma abiraterone and its metabolites levels were analyzed using a validated liquid chromatography–mass spectrometry method. Using calculated Cmin values of abiraterone and its active metabolite Δ(4)-abiraterone (D4A), univariate, and multivariable Cox regression analyses were performed. Results: Sixty-two patients were included in this retrospective analysis, of which 42% were underexposed (mean abiraterone Cmin ≤ 8.4 ng/mL). In multivariable analysis, Cmin ≥ 8.4 ng/mL was associated with longer prostate-specific antigen (PSA) independent progression-free survival (16.9 vs 6.1 months; p = 0.033), which resulted in a hazard ratio of 0.44 (95% confidence interval: 0.23–0.82, p = 0.01). D4A Cmin did not show a relationship with treatment efficacy. Conclusion: Our study shows that mCRPC patients with an abiraterone Cmin ≥ 8.4 ng/mL have a better prognosis compared with patients with low Cmin. Monitoring Cmin of abiraterone can help to identify those patients at risk of suboptimal treatment for whom treatment optimization may be appropriate.

Original languageEnglish
Pages (from-to)244-251
Number of pages8
JournalProstate Cancer and Prostatic Diseases
Volume23
Issue number2
DOIs
Publication statusPublished - 1 Jun 2020
Externally publishedYes

Fingerprint

Dive into the research topics of 'Exposure–response analyses of abiraterone and its metabolites in real-world patients with metastatic castration-resistant prostate cancer'. Together they form a unique fingerprint.

Cite this