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Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer

Authors :
Jean-Marc Ferrero
Hakim Mahammedi
Gwenaelle Gravis
Guilhem Roubaud
Philippe Beuzeboc
Remi Largillier
Delphine Borchiellini
Claude Linassier
Nathalie Ebran
Tanguy Pace-Loscos
Marie-Christine Etienne-Grimaldi
Renaud Schiappa
Jocelyn Gal
Gérard Milano
Source :
Pharmaceutics, Vol 15, Iss 2, p 651 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Abiraterone acetate (AA) is the first-in-class of drugs belonging to the second-generation of agents inhibiting androgen neosynthesis in advanced prostate cancer. A cumulative experience attests that germinal gene polymorphisms may play a role in the prediction of anticancer agent pharmacodynamics variability. In the present prospective, multicentric study, gene polymorphisms of CYP17A1 (AA direct target) and the androgen transporter genes SLCO2B1 and SLCO1B3 (potential modulators of AA activity) were confronted with AA pharmacodynamics (treatment response and toxicity) in a group of 137 advanced prostate cancer patients treated in the first line by AA. The median follow-up was 56.3 months (95% CI [52.5–61]). From multivariate analysis, rs2486758 C/C (CYP17A1) and PSA (≥10 ng/mL) were associated with a shorter 3-year biological PFS (HR = 4.05, IC95% [1.46–11.22]; p = 0.007 and HR = 2.08, IC95% [1.31–3.30]; p = 0.002, respectively). From a multivariate analysis, the rs743572 (CYP17A1) and performance status were independently associated with significant toxicity (OR = 3.78 (IC95% [1.42–9.75]; p = 0.006 and OR = 4.54; IC95% [1.46–13.61]; p = 0.007, respectively). Host genome characteristics may help to predict AA treatment efficacy and identify patients at risk for toxicity.

Details

Language :
English
ISSN :
19994923
Volume :
15
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.04920b18f914032b1945806680881d4
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics15020651