Germline variant in SLCO2B1 and response to abiraterone acetate plus prednisone (AA) in men with metastatic castration-resistant prostate cancer (mCRPC)
| Autor: | Neeraj Agarwal, David Gill, Darshan P. Patel, Austin Poole, Benjamin L. Maughan, Lisa A. Cannon-Albright, Andrew W. Hahn, James M. Farnham, Camryn Froerer, Peter Hale, Roberto Nussensveig |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty business.industry Abiraterone acetate Single-nucleotide polymorphism medicine.disease Androgen deprivation therapy chemistry.chemical_compound Prostate cancer chemistry Prednisone Internal medicine Genotype medicine Clinical endpoint business Genotyping medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 36:311-311 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 311 Background: Currently, there are no predictive biomarkers of response to AA in mCRPC routinely used in the clinic. SLCO2B1 encodes a sodium-independent organic anion transporter that mediates transport of endogenous sex hormones and drugs, including AA, into tissue. Single nucleotide polymorphisms (SNPs) in SLCO2B1 are a validated predictive biomarker of response to androgen deprivation therapy in hormone sensitive prostate cancer. In a recent pre-clinical study, the AA/AG genotype for rs12422149 and the AA genotype for rs1789693 of SLCO2B1 had significantly higher mean tissue abiraterone levels. We hypothesize that the variant allele for rs12422149 and rs1789693 are predictive of improved response to AA in mCRPC. Methods: Clinical data and samples were analyzed from a prospective prostate cancer registry at the University of Utah (Salt Lake City, UT). Genotyping was performed using the Illumina OmniExpress genotyping platform. Primary endpoint was progression-free survival (PFS) on first-line AA in men with mCRPC. We performed pre-specified multivariate Cox regression analyses to assess the independent predictive value of SLCO2B1 rs12422149 and rs1789693 on PFS on AA (table). Results: 76 men with mCRPC treated with first-line AA were included. In a multivariate analysis for rs12422149, a trend towards improved median PFS was seen with the AG genotype (11.2 months) vs. the GG genotype (6.4 months) (HR 0.50, 95% CI 0.24-1.02, p=0.056). No such correlation was seen with rs1789693 genotypes. Conclusions: Consistent with pre-clinical studies, the AG genotype in rs12422149 of SLCO2B1 may be predictive of response to AA in men with mCRPC. This hypothesis-generating data needs further interrogation in larger and independent cohorts. [Table: see text] |
| Databáze: | OpenAIRE |
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