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

被引：290

作者：

Armstrong, Andrew J. ^{[1
]}

Halabi, Susan ^{[1
]}

Luo, Jun ^{[2
]}

Nanus, David M. ^{[3
]}

Giannakakou, Paraskevi ^{[3
]}

Szmulewitz, Russell Z. ^{[4
]}

Danila, Daniel C. ^{[3
,5
]}

Healy, Patrick ^{[1
]}

Anand, Monika ^{[1
]}

Rothwell, Colin J. ^{[1
]}

Rasmussen, Julia ^{[1
]}

Thornburg, Blair ^{[1
]}

Berry, William R. ^{[1
]}

Wilder, Rhonda S. ^{[1
]}

Lu, Changxue ^{[2
]}

Chen, Yan ^{[2
]}

Silberstein, John L. ^{[2
]}

Kemeny, Gabor ^{[1
]}

Galletti, Giuseppe ^{[3
]}

Somarelli, Jason A. ^{[1
]}

Gupta, Santosh ^{[1
]}

Gregory, Simon G. ^{[1
]}

Scher, Howard I. ^{[3
,5
]}

Dittamore, Ryan ^{[6
]}

Tagawa, Scott T. ^{[3
]}

Antonarakis, Emmanuel S. ^{[2
]}

George, Daniel J. ^{[1
]}

机构：

[1] Duke Univ, Durham, NC USA

[2] Johns Hopkins Univ, Baltimore, MD USA

[3] Weill Cornell Med Coll, New York, NY USA

[4] Univ Chicago, Chicago, IL 60637 USA

[5] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[6] Epic Sci, San Diego, CA USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2019年 / 37卷 / 13期

关键词：

CIRCULATING TUMOR-CELLS; PROGNOSTIC MODEL; CLINICAL-TRIALS; ABIRATERONE; SURVIVAL; ENZALUTAMIDE; MEN; TESTOSTERONE; GENES; AR-V7;

D O I：

10.1200/JCO.18.01731

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

PURPOSE 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. PATIENTS AND METHODS 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. RESULTS 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; P = .032] and 2.4 [95% CI, 1.1 to 5.1; P = .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%. CONCLUSION 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. (C) 2019 by American Society of Clinical Oncology

引用

页码：1120 / +

页数：11

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