Abstract
Androgen receptor splice variant-7 (AR-V7) expression in circulating tumor cells (CTCs) in metastatic castration-resistant prostate cancer (mCRPC) is associated with abiraterone and enzalutamide resistance. We determine whether cabazitaxel (CBZ) is equally effective in AR-V7-positive and -negative CRPC and whether AR-V7-positive patients retain CBZ sensitivity. This is the first prospective, open-label, Asian validation study of CBZ in Japanese patients with mCRPC after docetaxel (n = 48; four CBZ cycles; 2017-2020, Juntendo University Hospitals). Primary endpoint was prostate-specific antigen response rate (PSA-RR); secondary endpoints included overall survival (OS), bone scan index (BSI) PSA-RR (≥ 50% decline from baseline) for CTC-/ARV7-, CTC+ /ARV7-, and CTC +/ARV7+ groups. PSA-RR ≥ - 30% was 38% (18/48) and ≥ - 50% was 26% (12/48). BSI-change rate ≥ - 30% was 19% (9/41) and ≥ - 50% was 17% (8/41). Median OS was 13.7(12.2-18.9) months. PSA decline in early CBZ treatment associated with OS (p = 0.00173). BSI decline associated with OS (p = 0.0194). PSA-RR(≥ 50%) was 43%(6/14) in CTC-/ARV7-, 19%(5/26) in CTC+ ARV7-, and 12%(1/8) in CTC+/ARV7+ ( p > 0.05). AR-V7 in CTCs at baseline not associated with OS. AR-V7 was not associated with CBZ resistance in CTCs. Reductions in BSI and PSA in early stages of CBZ treatment may predict OS.