3301 - Implications of Single Nucleotide Polymorphisms (SNPs) in Androgen Related-Genes in Outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with Abiraterone (Abi) and Enzalutamide (Enza)

Background

Different therapeutic options have been approved in the last decade for the management of mCRPC. New prognosis biomarkers are necessary in the clinical practice to determine the optimal treatment sequence. In recent years, a number of studies have suggested an association between SNPs in androgen related-genes and outcome.

Methods

Abi or Enza-treated mCRPC patients (pts) in the PROREPAIR-B study (NCT03075735) were included. Nine SNPs within the six candidate genes, namely, CYP17A1 (rs2486758), SCLO2B1 (rs1077858), SRD5A1 (rs3736316 and rs3822430), SRD5A2 (rs2300700), HSD3B1 (rs1047303) and SULT1E1 (rs10019305, rs4149534 and rs3775777) were genotyped. Genotyping was performed using predesigned and custom Taqman SNP genotyping assays (Applied Biosystems, Foster City, CA) and 7500 Fast Real-Time PCR systems (Applied Biosystems, Foster City, CA). The allele calls were identified by specific software. Associations between genotypes and overall survival (OS), time to PSA progression (TTPP) and time to castration resistance (TCR) were calculated with bivariate Cox-regression models including line of treatment. Kaplan Meier estimates of survival were calculated.

Results

322 pts treated with Abi (n = 259; 80.4%) or Enza (n = 63; 19.6%) were included in the analysis. Pts received Abi/Enza as first (n = 209; 64.9%), second (n = 111; 34.5%) or third (n = 2; 0.6%) line. Median OS was 25.9 m (95% CI: 23.5-28.3); median TTPP was 7 m (95% CI: 6.1-7.9) and median TCR was 29.1 m (95% CI: 24.1-34.1). rs3822430 SRD5A1 (0.82 [95% CI: 0.72-0.95]; p = 0.007) an rs3736316 SRD5A1 (HR: 0.86 [0.74-0.99]; p = 0.033) showed a significant association with OS. rs2486758 CYP17A1 (HR: 0.78 [0.64-0.95]; p = 0.014) showed a significant association with TCR. No SNPs showed an association with TTPP.

Conclusions

In our series (PROREPAIR-B) not significant associations were observed between most of the evaluated SNPs and outcomes in mCRPC patients treated with Abi or Enza.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Centro Nacional de Investigaciones Oncológicas (CNIO).

Funding

Has not received any funding.

Disclosure

D. Lorente: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas Pharma; Travel / Accommodation / Expenses: Celgene. R. Lozano Mejorada: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen-Cilag; Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Astellas-Pharma. N. Romero Laorden: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas-Pharma; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen-Cilag; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi-Aventis; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: PharmaMar; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche. A. Medina Colmenero: Honoraria (self), Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self): Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Janssen-Cilag; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Novartis. J. Puente: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy: Kiowa; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eusa Pharma; Advisory / Consultancy: Boehringer Ingelheim. R. Villatoro: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas-Pharma; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol. S. Vazquez Estevez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. J.M. Piulats: Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen Oncology; Advisory / Consultancy: Astella Pharma; Advisory / Consultancy: VCN Biosciences; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Clovis Oncology; Research grant / Funding (self): Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Research grant / Funding (self): Incyte; Research grant / Funding (self): MedImmune; Research grant / Funding (self): EMD Serono; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb. N. Lainez: Advisory / Consultancy: Astellas-Pharma; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer. A. González del Alba: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Astellas-Pharma; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen Oncology; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: MSD Oncology; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy: EUSA Pharma; Advisory / Consultancy: Ipsen; Full / Part-time employment: SERMAS. D. Olmos Hidalgo: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self): Sanofi; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Clovis Oncology; Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Tokai Pharmaceuticals. E. Castro: Honoraria (self), Travel / Accommodation / Expenses: Astellas-Pharma; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.