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

被引：57

作者：

Armstrong, Andrew J. ^{[1
]}

Luo, Jun ^{[2
]}

Nanus, David M. ^{[3
]}

Giannakakou, Paraskevi ^{[3
]}

Szmulewitz, Russell Z. ^{[4
]}

Danila, Daniel C. ^{[3
,5
,6
]}

Healy, Patrick

Anand, Monika ^{[1
]}

Berry, William R. ^{[1
]}

Zhang, Tian ^{[1
]}

Harrison, Michael R. ^{[1
]}

Lu, Changxue ^{[2
]}

Chen, Yan ^{[2
]}

Galletti, Giuseppe ^{[3
]}

Schonhoft, Joseph D. ^{[7
]}

Scher, Howard I. ^{[5
,6
]}

Wenstrup, Richard ^{[7
]}

Tagawa, Scott T. ^{[3
]}

Antonarakis, Emmanuel S. ^{[2
,8
]}

George, Daniel J. ^{[1
]}

Halabi, Susan ^{[8
]}

机构：

[1] Duke Univ, Dept Med, Duke Canc Inst, Ctr Prostate & Urol Canc, Durham, NC USA

[2] Johns Hopkins Univ, Dept Urol, 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] Parexel, Durham, NC USA

[7] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA

[8] Duke Univ, Dept Biostat & Bioinforamt, Durham, NC USA

来源：

JCO PRECISION ONCOLOGY | 2020年 / 4卷

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1200/PO.20.00200

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSEAndrogen 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 METHODSPROPHECY 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.RESULTSWe 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.CONCLUSIONDetection 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.

引用

页码：1285 / 1301

页数：17

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