Circulating tumor cell gene expression and plasma AR gene copy number as biomarkers for castration-resistant prostate cancer patients treated with cabazitaxel

Background Cabazitaxel improves overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients progressing after docetaxel. In this prospective study, we evaluated the prognostic role of CTC gene expression on cabazitaxel-treated patients and its association with plasma androgen receptor ( AR ) copy number (CN). Methods Patients receiving cabazitaxel 20 or 25 mg/sqm for mCRPC were enrolled. Digital PCR was performed to assess plasma AR CN status. CTC enrichment was assessed using the AdnaTest EMT-2/StemCell kit. CTC expression analyses were performed for 17 genes. Data are expressed as hazard ratio (HR) or odds ratio (OR) and 95% CI. Results Seventy-four patients were fully evaluable. CTC expression of AR-V7 (HR=2.52, 1.24–5.12, p =0.011), AKR1C3 (HR=2.01, 1.06–3.81, p =0.031), AR (HR=2.70, 1.46–5.01, p =0.002), EPCAM (HR=3.75, 2.10–6.71, p < 0.0001), PSMA (HR=2.09, 1.19–3.66, p =0.01), MDK (HR=3.35, 1.83–6.13, p < 0.0001), and HPRT1 (HR=2.46, 1.44–4.18, p =0.0009) was significantly associated with OS. ALDH1 (OR=5.50, 0.97–31.22, p =0.05), AR (OR=8.71, 2.32–32.25, p =0.001), EPCAM (OR=7.26, 1.47–35.73, p =0.015), PSMA (OR=3.86, 1.10–13.50, p =0.035), MDK (OR=6.84, 1.87–24.98, p =0.004), and HPRT1 (OR=7.41, 1.82–30.19, p =0.005) expression was associated with early PD. AR CN status was significantly correlated with AR-V7 ( p =0.05), EPCAM ( p =0.02), and MDK ( p =0.002) expression. In multivariable model, EPCAM and HPRT1 CTC expression, plasma AR CN gain, ECOG PS=2, and liver metastases and PSA were independently associated with poorer OS. In patients treated with cabazitaxel 20 mg/sqm, median OS was shorter in AR-V7 positive than negative patients (6.6 versus 14 months, HR=3.46, 1.47–8.17], p =0.004). Conclusions Baseline CTC biomarkers may be prognosticators for cabazitaxel-treated mCRPC patients. Cabazitaxel at lower (20 mg/sqm) dose was associated with poorer outcomes in AR-V7 positive patients compared to AR-V7 negative patients in a post hoc subgroup analysis. Trial registration Clinicaltrials.gov NCT03381326 . Retrospectively registered on 18 December 2017.