Association of single nucleotide polymorphisms (SNPs) in CYP17A1 and SLCO2B1 genes and clinical outcome in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: results of the ABIGENE prospective study.

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358 Background: Abiraterone acetate (AA), a CYP17A1 inhibitor, has been approved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Germline polymorphisms in genes involved in androgen biosynthesis or transport may influence response and survival in this setting. Methods: ABIGENE is a multicentric prospective non-randomized pharmacogenetic study (NCT01858441). The primary objective was to investigate the association between 13 SNPs in genes related to AA pharmacology (CYP17A1, SLCO2B1 and SLCO2B3) and radiographic progression-free survival (rPFS), according to PCWG2 criteria, in pts with mCRPC treated with first-line AA + prednisone. The main secondary objectives were to evaluate the impact of these SNPs on radiographic and PSA response, overall survival (OS) and toxicity. SNPs were detected in blood samples before starting AA and analyzed by pyrosequencing or PCR-RFLP methods. Kaplan-Meyer’s curves with log-rank tests and cox regression models were used to identify relationships between SNPs and survival. Chi2 tests and student t-tests were used to identify association with response rate and toxicity. Results: 147 pts in 17 french centers were included between 2013 and 2017. Here are presented the results for the first 109 pts. The median follow-up was 28.7 months. Overall response rate (ORR) was 17%, and 74% pts had stable disease as the best response. Median rPFS was 10.9 months (95% CI 9.2-15.3). One SNP (rs10883782) in CYP17A1 was associated with rPFS on AA therapy (Table). Two other SNPs in CYP17A1 (rs4919683) and SLCO2B1 (rs1077858) were significantly associated with radiographic response. Data on PSA response, OS and toxicity will be presented at the meeting. Conclusions: This is the first prospective dedicated study to show an association between SNPs related to androgen metabolism and clinical outcome in mCRPC treated with AA. Clinical trial information: NCT01858441. [Table: see text]