Details

Autor(en) / Beteiligte

• Armstrong, Andrew J
• Halabi, Susan
• Luo, Jun
• Nanus, David M
• Giannakakou, Paraskevi
• Szmulewitz, Russell Z
• Danila, Daniel C
• Healy, Patrick
• Anand, Monika
• Rothwell, Colin J
• Rasmussen, Julia
• Thornburg, Blair
• Berry, William R
• Wilder, Rhonda S
• Lu, Changxue
• Chen, Yan
• Silberstein, John L
• Kemeny, Gabor
• Galletti, Giuseppe
• Somarelli, Jason A
• Gupta, Santosh
• Gregory, Simon G
• Scher, Howard I
• Dittamore, Ryan
• Tagawa, Scott T
• Antonarakis, Emmanuel S
• George, Daniel J

Titel

Prospective Multicenter Validation of Androgen Receptor Splice Variant 7 and Hormone Therapy Resistance in High-Risk Castration-Resistant Prostate Cancer: The PROPHECY Study

Ist Teil von

• Journal of clinical oncology, 2019-05, Vol.37 (13), p.1120-1129

Ort / Verlag

United States: American Society of Clinical Oncology

Erscheinungsjahr

2019

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Androgen receptor splice variant 7 (AR-V7) results in a truncated receptor, which leads to ligand-independent constitutive activation that is not inhibited by anti-androgen therapies, including abiraterone or enzalutamide. Given that previous reports suggested that circulating tumor cell (CTC) AR-V7 detection is a poor prognostic indicator for the clinical efficacy of secondary hormone therapies, we conducted a prospective multicenter validation study. PROPHECY ( ClinicalTrials.gov identifier: NCT02269982) is a multicenter, prospective-blinded study of men with high-risk mCRPC starting abiraterone acetate or enzalutamide treatment. The primary objective was to validate the prognostic significance of baseline CTC AR-V7 on the basis of radiographic or clinical progression free-survival (PFS) by using the Johns Hopkins University modified-AdnaTest CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear-specific AR-V7 protein assay. Overall survival (OS) and prostate-specific antigen responses were secondary end points. We enrolled 118 men with mCRPC who were starting abiraterone or enzalutamide treatment. AR-V7 detection by both the Johns Hopkins and Epic AR-V7 assays was independently associated with shorter PFS (hazard ratio, 1.9 [95% CI, 1.1 to 3.3; = .032] and 2.4 [95% CI, 1.1 to 5.1; = .020], respectively) and OS (hazard ratio, 4.2 [95% CI, 2.1 to 8.5] and 3.5 [95% CI, 1.6 to 8.1], respectively) after adjusting for CTC number and clinical prognostic factors. Men with AR-V7-positive mCRPC had fewer confirmed prostate-specific antigen responses (0% to 11%) or soft tissue responses (0% to 6%). The observed percentage agreement between the two AR-V7 assays was 82%. Detection of AR-V7 in CTCs by two blood-based assays is independently associated with shorter PFS and OS with abiraterone or enzalutamide, and such men with mCRPC should be offered alternative treatments.