Efficacy of cabazitaxel and androgen splicing variant-7 status in circulating tumor cells in Asian patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Androgen receptor splice variant-7(AR-V7) expression in circulating tumor cells(CTCs) in metastatic castration-resistant prostate cancer (mCRPC) is associated with resistance to abiraterone and enzalutamide. We had objectives to determine whether cabazitaxel(CBZ) was equally effective in AR-V7 positive and negative CRPC, and if AR-V7 positive patients retained CBZ sensitivity. METHODS: This study was first-of-a-kind, Asian validation, prospective, open-label study: CBZ in Japanese mCRPC patients after docetaxel. 48 patients completed 4 CBZ cycles (recruited: 2017–2020, Juntendo University Hospitals). Primary endpoint was prostate-specific antigen response rate(PSA-RR), and secondary endpoints were overall survival(OS), Bone Scan Index[BSI]-change rate of bone metastases by bone scintigraphy, and safety assessments. PSA-RR(≥50% decline from baseline) for: CTC-/ARV7-, CTC+/ARV7-, CTC+/AR+ groups. RESULTS: PSA-RR shown ≥30% was 38%(18/48) and ≥50% was 26%(12/48). BSI-change rate shown ≥-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 21%(3/14) in CTC-/ARV7- group, 16%(4/25) in CTC+/ARV7- and 12%(1/8) in CTC+/ARV7+. No statically significant differences between groups. AR-V7 in CTCs at baseline not associated with OS. CONCLUSIONS: AR-V7 in CTCs was not associated with resistance to CBZ. BSI and PSA reducing responses in early CBZ may predict OS.