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

Pharmacogenomics 2022 Jul

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Background: 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). Patients & methods: 56 SNPs in five genes (CYP3A4, CYP3A5, ABCB1, TUBB1 and CYP2C8) were genotyped in 67 mCRPC patients and their correlation with outcomes analyzed. Results:TUBB1-rs151352 (hazard ratio: 0.52) and CYP2C8-rs1341164 (hazard ratio: 0.53) were associated with better overall survival, and CYP2C8-rs1058932 with biochemical progression (odds ratio: 6.60) in multivariate analysis. ABCB1-rs17327624 correlated with severe toxicity ≥grade 3 (odds ratio: 8.56) and CYP2C8-rs11572093 with asthenia (odds ratio: 8.12). Conclusion: 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.

Citation

Daniel Herrero Rivera, Carmen Garrigós Vacas, Laura Marcos Kovandzic, Javier Puente Vázquez, Lucía A Alonso, Begoña Mellado González, Verónica Calderero Aragón, Enrique Grande, Raquel Luque Caro, Juan A Virizuela Echaburu, Juan F Rodríguez Moreno, Ainara A Etxebarria, Cristina Rodríguez-Antona, Ignacio Durán. Single-nucleotide polymorphism associations with efficacy and toxicity in metastatic castration-resistant prostate cancer treated with cabazitaxel. Pharmacogenomics. 2022 Jul;23(11):627-638