Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients

E Carton; G Noe; O Huillard; L Golmard; J Giroux; A Cessot; N E B Saidu; M Peyromaure; M Zerbib; C Narjoz; J Guibourdenche; A Thomas; M Vidal; F Goldwasser; B Blanchet; J Alexandre

doi:10.1016/j.ejca.2016.11.027

Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients

Eur J Cancer. 2017 Feb:72:54-61. doi: 10.1016/j.ejca.2016.11.027. Epub 2016 Dec 24.

Authors

E Carton¹, G Noe², O Huillard³, L Golmard⁴, J Giroux³, A Cessot³, N E B Saidu³, M Peyromaure⁵, M Zerbib⁵, C Narjoz⁶, J Guibourdenche⁷, A Thomas², M Vidal², F Goldwasser³, B Blanchet², J Alexandre³

Affiliations

¹ Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France. Electronic address: carton.edith@gmail.com.
² Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
³ Department of Medical Oncology, Cochin Hospital, Paris Descartes University, CARPEM, AP-HP, Paris, France.
⁴ Department of Genetics, Institut Curie, Paris, France.
⁵ Department of Urology, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.
⁶ Biochemistry Unit, Georges Pompidou European Hospital, Paris Descartes University, AP-HP, Paris, France.
⁷ Hormonology Laboratory, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France.

PMID: 28027516
DOI: 10.1016/j.ejca.2016.11.027

Abstract

Background: Abiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity.

Patients and methods: This is a monocentric prospective observational study in mCRPC patients treated with ABI. The plasmatic concentration of ABI at steady state was measured using liquid chromatography with fluorescence detection. The primary objective was to study the relationship between mean ABI plasma exposure (ABI C_min) and 3-month PSA response.

Results: From 2012 to 2016, 61 mCRPC patients were eligible for pharmacokinetic/pharmacodynamic assessment. Thirty-eight patients experienced PSA response (62%, [confidence interval {CI} 95% 50-78]). In univariate analysis, ABI C_min was 1.5-fold higher in responders: 12.0 ng/mL (CI 95% 9.4-15.6) versus 8.0 ng/mL (CI 95% 5.8-11.6; P = 0.0015). In multivariate analysis, only ABI C_min was independently associated with PSA response (odds ratio = 1.12 [CI 95% 1.01-1.25], P = 0.004). By receiver operating characteristic analysis, the optimal threshold for ABI C_min was 8.4 ng/mL. Progression-free survival (PFS) was significantly higher in patients with ABI C_min above 8.4 ng/mL (hazard ratio 0.55, [CI 95% 0.31-0.99], 12.2 [CI 95% 9.2-19.5] versus 7.4 [CI 95% 5.5-14.7] months otherwise, P = 0.044).

Conclusions: We showed that ABI trough concentration correlates with PSA response and PFS. Moreover, we could determine a cut-off value of plasmatic concentration for PSA response. Altogether, ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients.

Keywords: Abiraterone acetate; Drug monitoring; Metastatic castration-resistant prostate carcinoma; PSA response; Trough concentration.

Publication types

Observational Study

MeSH terms

Aged
Aged, 80 and over
Androgen Antagonists / blood
Androgen Antagonists / pharmacokinetics*
Androgen Antagonists / therapeutic use
Androstenes / blood
Androstenes / pharmacokinetics*
Androstenes / therapeutic use
Disease-Free Survival
Humans
Kaplan-Meier Estimate
Logistic Models
Male
Prospective Studies
Prostate-Specific Antigen / blood*
Prostatic Neoplasms, Castration-Resistant / blood
Prostatic Neoplasms, Castration-Resistant / drug therapy*

Substances

Androgen Antagonists
Androstenes
Prostate-Specific Antigen
abiraterone