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- W3203864694 abstract "Cabazitaxel showed overall survival (OS) benefit for mCRPC patients (pts) progressing after docetaxel. In a prospective study (NCT03381326), we evaluated the role of CTC gene expression of cabazitaxel-treated pts and its association with plasma AR CN. We enrolled 100 mCRPC pts receiving cabazitaxel 20 or 25 mg/sqm from December 2014 to December 2018. Baseline plasma DNA was isolated and digital PCR was performed to assess AR CN status. CTC enrichment was assessed using AdnaTest EMT-2/StemCell kit. CTC expression analyses were performed for 17 genes. Seventy-four pts were fully evaluable for this analysis. CTC expression of AR-V7 (hazard ratio [HR]=2.52, 95% CI 1.24-5.12, p=0.011), AKR1C3 (HR=2.01, 95% CI 1.06-3.81, p=0.031), AR (HR=2.70, 95% CI 1.46-5.01, p=0.002), EPCAM (HR=3.75, 95% CI 2.10-6.71, p<0.0001), PSMA (HR=2.09, 95% CI 1.19-3.66, p=0.01), MDK (HR=3.35, 95% CI 1.83-6.13, p<0.0001) and HPRT1 (HR=2.46, 95% CI 1.44-4.18, p=0.0009) was associated with shorter OS in univariate analysis. ALDH1 (odds ratio [OR]=5.50, 95% CI 0.97-31.22, p=0.05), AR (OR=8.71, 95% CI 2.32-32.25, p=0.001), EPCAM (OR=7.26, 95% CI 1.47-35.73, p=0.015), PSMA (OR=3.86, 95% CI 1.10-13.50, p=0.035), MDK (OR=6.84, 95% CI 1.87-24.98, p=0.004) and HPRT1 (OR=7.41, 95% CI 1.82-30.19, p=0.005) expression was associated with early disease progression within the first three months. AR CN status was correlated with AR-V7 (p=0.05), EPCAM (p=0.02) and MDK (p=0.002) expression. Using a multivariable model, EPCAM CTC expression, AR CN gain, ECOG PS ≥ 2 and liver metastases were independently associated with poorer OS. In pts treated with cabazitaxel 20 mg/sqm, a shorter median OS was observed in AR-V7-pos pts (n=8) than AR-V7-neg (n=36) (6.6 versus 14 months, HR=3.46, 95% CI 1.47-8.17, p=0.004). No significant difference was found between those patients treated with cabazitaxel 25 mg/sqm (p=0.839). Baseline CTC biomarkers may be considered useful prognosticators for cabazitaxel-treated mCRPC pts. Our results suggest that cabazitaxel 25 mg/sqm should be preferred in AR-V7-pos mCRPC." @default.
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- W3203864694 date "2021-09-01" @default.
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- W3203864694 title "615P Circulating tumor cells (CTC) gene expression and plasma androgen receptor (AR) copy number (CN) in cabazitaxel-treated metastatic castration-resistant prostate cancer (mCRPC)" @default.
- W3203864694 doi "https://doi.org/10.1016/j.annonc.2021.08.1128" @default.
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