Prospective Multicenter Study of Circulating Tumor Cell AR-V7 and Taxane Versus Hormonal Treatment Outcomes in Metastatic Castration-Resistant Prostate Cancer.

Journal Article (Journal Article)

PURPOSE: Androgen receptor splice variant 7 (AR-V7) detection in circulating tumor cells (CTCs) is associated with a low probability of response and short progression-free (PFS) and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide or abiraterone. However, it is unclear whether such men benefit from taxane chemotherapy. PATIENTS AND METHODS: PROPHECY is a multicenter prospective blinded study of patients with poor-risk mCRPC starting abiraterone or enzalutamide and observed through subsequent progression and taxane chemotherapy. We assessed AR-V7 status using the Johns Hopkins modified AdnaTest CTC AR-V7 messenger RNA assay and the Epic Sciences CTC nuclear-localized AR-V7 protein assay before treatment. The primary objective was to validate the independent prognostic value of CTC AR-V7 status based on radiographic/clinical PFS. OS, confirmed prostate-specific antigen (PSA), and objective radiologic responses were secondary end points. RESULTS: We enrolled 118 men with mCRPC treated with abiraterone or enzalutamide, 51 of whom received subsequent docetaxel or cabazitaxel. Pretreatment CTC AR-V7 status by the Johns Hopkins and Epic Sciences assays was independently associated with worse PFS (hazard ratio [HR], 1.7; 95% CI, 1.0 to 2.9 and HR, 2.1; 95% CI, 1.0 to 4.4, respectively) and OS (HR, 3.3; 95% CI, 1.7 to 6.3 and HR, 3.0; 95% CI, 1.4 to 6.3, respectively) and a low probability of confirmed PSA responses, ranging from 0% to 11%, during treatment with abiraterone or enzalutamide. At progression, subsequent CTC AR-V7 detection was not associated with an inferior PSA or radiographic response or worse PFS or OS with subsequent taxane chemotherapy after adjusting for CellSearch CTC enumeration and clinical prognostic factors. CONCLUSION: Detection of AR-V7 in CTCs by two different blood-based assays is independently associated with shorter PFS and OS with abiraterone or enzalutamide, but such men with AR-V7-positive disease still experience clinical benefits from taxane chemotherapy.

Full Text

Duke Authors

Cited Authors

  • Armstrong, AJ; Luo, J; Nanus, DM; Giannakakou, P; Szmulewitz, RZ; Danila, DC; Healy, P; Anand, M; Berry, WR; Zhang, T; Harrison, MR; Lu, C; Chen, Y; Galletti, G; Schonhoft, JD; Scher, HI; Wenstrup, R; Tagawa, ST; Antonarakis, ES; George, DJ; Halabi, S

Published Date

  • 2020

Published In

Volume / Issue

  • 4 /

PubMed ID

  • 33154984

Pubmed Central ID

  • 33154984

Electronic International Standard Serial Number (EISSN)

  • 2473-4284

Digital Object Identifier (DOI)

  • 10.1200/PO.20.00200

Language

  • eng

Conference Location

  • United States