期刊
JOURNAL OF CLINICAL ONCOLOGY
卷 37, 期 13, 页码 1120-+出版社
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.18.01731
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资金
- Prostate Cancer Foundation and Movember
- Prostate Cancer Foundation
- Duke Cancer Institute [P30 CA014236]
- Duke Cancer Institute
- Department of Defense [W81XWH-13-PCRP-CCA, W81XWH-17-2-0021, W81XWH-14-2-0179, W81XWH-14-2-0159, W81XWH-15-2-0018, W81XWH-16-PCRP-CCRSA]
- National Cancer Institute [P30 CA008748, T32 CA062948]
- Memorial Sloan Kettering Cancer Center
- Sidney Kimmel Center for Prostate and Urologic Cancers
- Clinical and Translational Science Center [P30 CA014236, UL1 TR002384-01]
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
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