Single-nucleotide polymorphismassociations with efficacy and toxicity in metastatic castration-resistant prostate cancer treated with cabazitaxel.

Abstract

<b>Background:</b> The aim of this study was to evaluate the impact of certain single-nucleotide polymorphisms (SNPs) in cabazitaxel activity and toxicity in patients with metastatic castration-resistant prostate cancer (mCRPC). <b>Patients &amp; methods:</b> 56 SNPs in five genes (<i>CYP3A4</i>, <i>CYP3A5</i>, <i>ABCB1</i>, <i>TUBB1</i> and <i>CYP2C8</i>) were genotyped in 67 mCRPC patients and their correlation with outcomes analyzed. <b>Results:</b><i>TUBB1</i>-rs151352 (hazard ratio: 0.52) and <i>CYP2C8</i>-rs1341164 (hazard ratio: 0.53) were associated with better overall survival, and <i>CYP2C8</i>-rs1058932 with biochemical progression (odds ratio: 6.60) in multivariate analysis. <i>ABCB1</i>-rs17327624 correlated with severe toxicity ≥grade 3 (odds ratio: 8.56) and <i>CYP2C8</i>-rs11572093 with asthenia (odds ratio: 8.12). <b>Conclusion:</b> Genetic variants in mCRPC patients could explain different outcomes with cabazitaxel. Nonetheless, the small sample size and the high number of SNPs analyzed mean that the results are only hypothesis-generating and require further validation.