Cabazitaxel (CBZ) has been shown to improve overall survival (OS) in metastatic castration resistant prostate cancer (mCRPC) patients (pts) and to overcome resistance to docetaxel (DOC). Circulating tumor cells (CTCs) can be useful tool for precision medicine. CTCs expression profiling before CBZ treatment could establish novel predictive biomarkers.
We prospectively enrolled 28 pts with mCRPC treated with CBZ 25 mg/mq q21 after DOC and abiraterone or enzalutamide. CTCs enrichment was assessed with Adna Test EMT/STEM. Expression analyses of AKR1C3, AKT2, ALDH1, AR, ARV7, EPCAM, FOLH1, MDK, PARP, MRP1, PIK3CA, POU5F1, PSCA, TUBB3, VIM, ACT, HPRT1 were analyzed using real time PCR. CTCs positive pts were defined when at least one marker among AKT2, AR, AR-V7, EPCAM, FOLH1, PSCA, PIK3CA was expressed. Progressive disease was defined according to PCWG2 criteria. Main endpoint was the correlation between CTCs expression profiling and outcome.
Of these 28 pts, 18 (64%) had detectable CTCs before the starting of CBZ and 10 (36%) had undetectable CTCs. Detection of CTCs was associated with poor OS. However, no difference was observed for progression free survival (PFS). No correlation between CTCs assessment and PSA response rate was found. In addition, we subdivided pts according to median value of CTCs expression markers. Nine (50%) pts with ≥3 markers had a significant worse PFS compared to pts with
We prospectively confirmed a prognostic role for CTCs in mCRPC pts treated with CBZ and we also firstly showed the utility to characterize CTCs expression markers thanks to its potential predictive role. The identification of markers expressed on CTCs may also provide additional therapeutic targets. More details on the prognostic impact of these biomarkers and AR status and mutations are under analysis and will be presented at meeting.
Clinical trial identification
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Ugo De Giorgi
All authors have declared no conflicts of interest.