Background: The organic anion transport polypeptide SLCO1B3 is expressed on both hepatocytes and CRPC tumor cells and mediates docetaxel transport. Preclinically, loss of expression of SLCO1B3 on tumor cells has been shown to confer taxane resistance. We hypothesized that SNPs in SLCO1B3 can also affect docetaxel transport and thus, its efficacy. Through this retrospective institutional analysis, we evaluated the impact of SLCO1B3 genotype on outcomes in CRPC patients treated with docetaxel. Methods: The study included CRPC patients treated with docetaxel who underwent genotyping for a previously identified SNP in SLCO1B3 (rs4149117; Yang et al JCO 2011). Associations of SNP with PSA response (≥50% decline from baseline), time to treatment failure (TTTF: time from docetaxel initiation to start of next therapy or death from any cause) and overall survival (OS) were evaluated in multivariable logistic and Cox regression models, adjusted for known prognostic factors. Results:SLCO1B3 genotyping and follow up data were available for 289 CRPC patients. The most common rs4149117 genotype was GG (67%; n = 194) followed by GT (29%; n = 84) and TT (4%; n = 11). The rs4149117 GT/TT > GG genotype was associated with improved TTTF (median 8.9 vs. 6.7 mos; hazard ratio: 0.69; 95%CI: 0.53-0.90; P = 0.007). There was no significant difference among the genotypes in terms of PSA response rate or OS (Table). Conclusions: Our findings suggest that the SLCO1B3 genotype could impact clinical outcomes in CRPC patients treated with docetaxel. Additional studies are needed to evaluate both SLCO1B3 genotype and its expression on tumor cells as pharmacogenomic predictors of outcomes in CRPC.

*Adjusted for biopsy Gleason, type of primary therapy, prior abiraterone/enzalutamide use, metastatic status (none, bone/LN only or visceral), age and PSA at docetaxel initiation