Prospective analysis of AR-V7 expression in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) sequentially treated with docetaxel and enzalutamide.

250 Background: Androgen receptor splice variant 7 (AR-V7) has been associated with poor outcomes in mCRPC patients treated with androgen receptor pathway inhibitors (ARPI). However, its predictive value is still not clear. Methods: We conducted a prospective single-arm trial to evaluate the role of AR-V7 as a potential predictive biomarker for ARPI treatment. Patients were initially treated IV with docetaxel 75 mg/m2. Enzalutamide 160 mg daily PO was started upon progression. Blood samples were harvested before docetaxel (C1), before enzalutamide (C2), and at the time of progression on enzalutamide (C3). Outcomes analyzed included PSA50 response (decline of 50% or more from baseline), PSA Progression-free Survival (PFS), and Overall Survival (OS) from the start of treatment. AR-V7 expression in circulating tumor cells was detected using AdnaTest Prostate Cancer Detect kit (Qiagen). Results: From October 2019 to July 2021, 30 patients were included. AR-V7 expression was detected in 40% of patients at C1, 46% at C2, and 74% at C3. All four patients who became AR-V7 positive at C2 responded to enzalutamide. The PSA50 to docetaxel was 33.3%. There was no significant difference in PSA50 between AR-V7pos and AR-V7neg patients at C1 (Table). The PSA50 to enzalutamide was 79.3%. Similarly, there was no significant difference in PSA50 between AR-V7pos and AR-V7neg at C2 (Table). The median PFS to docetaxel and enzalutamide were 6.0 mo and 15.0 mo, respectively. There was no significant difference in PFS to docetaxel between AR-V7pos and AR-V7neg patients at C1. PFS on enzalutamide was 9.0 mo for AR-V7pos and 20.0 mo for AR-V7neg patients at C2, but the difference was not statistically significant (Table). The median PFS to the sequential treatment and OS were 23.0 mo and 30.0 mo, respectively. AR-V7pos patients at C1 had shorter PFS to sequential treatment and shorter OS (Table). Conclusions: AR-V7 expression was not associated with response to docetaxel and enzalutamide but with shorter PFS and OS to sequential treatment. AR-V7 expression may be considered a prognostic, but not predictive, biomarker in mCRPC patients. Clinical trial information: NCT03700099 . AR-V7 status at C1 AR-V7 pos AR-V7 neg OR/HR (IC95%) p-value PSA50 to Docetaxel 33.3% 35.3% OR 1.90 (0.23-5.20) >0.999 * PFS on Docetaxel 5.0 mo 6.0 mo HR 1.73 (0.80-3.73) 0.164 # PFS on Doce + Enza 13.0 mo 28.0 mo HR 2.74 (1.16-6.50) 0.022 # OS 20.0 mo 41.0 mo HR 3.28 (1.30-8.27) 0.012 # AR-V7 status at C2 AR-V7 pos AR-V7 neg OR/HR (IC95%) p-value PSA50 to Enzalutamide 76.9% 80% OR 1.20 (0.20-7.31) >0.999 * PFS on Enzalutamide 9.0 mo 20.0 mo HR 1.95 (0.82-4.64) 0.131 # OR=odds ratio, HR=hazard ratio; * Fisher's exact test; # Kaplan Meier and Log-rank.