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

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.

 

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This paragraph describes a study that investigated the potential role of genetic variations in predicting the response and toxicity of abiraterone acetate (AA) treatment in advanced prostate cancer patients. The study focused on three genes: CYP17A1, SLCO2B1, and SLCO1B3, which are involved in androgen neosynthesis and transport, and thus potentially modulate AA activity. The study included 137 patients who were treated with AA as the first-line therapy, and the median follow-up was 56.3 months.

The study found that certain genetic variations were associated with AA treatment response and toxicity. Specifically, the C/C genotype of rs2486758 in CYP17A1 and PSA levels ≥10 ng/mL were associated with a shorter 3-year biological progression-free survival (PFS), while the rs743572 variant in CYP17A1 and performance status were independently associated with significant toxicity. These findings suggest that genetic testing may help identify patients who are likely to respond well to AA treatment and those who are at risk of developing toxicity. Overall, this study highlights the potential of personalized medicine in prostate cancer treatment.

Related Products

Cat.No. Product Name Information
S2246 Abiraterone Acetate Abiraterone Acetate is an acetate salt form of Abiraterone which is a steroidal cytochrome CYP17 inhibitor with IC50 of 72 nM in a cell-free assay. Abiraterone acetate is an oral androgen biosynthesis inhibitor.

Related Targets

P450 (e.g. CYP17) Androgen Receptor