Prospective multicenter validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer: The PROPHECY study Journal Article
| Authors: | Armstrong, A. J.; Halabi, S.; Luo, J.; Nanus, D. M.; Giannakakou, P.; Szmulewitz, R. Z.; Danila, D. C.; Healy, P.; Anand, M.; Rothwell, C. J.; Rasmussen, J.; Thornburg, B.; Berry, W. R.; Wilder, R. S.; Lu, C.; Chen, Y.; Silberstein, J. L.; Kemeny, G.; Galletti, G.; Somarelli, J. A.; Gupta, S.; Gregory, S. G.; Scher, H. I.; Dittamore, R.; Tagawa, S. T.; Antonarakis, E. S.; George, D. J. |
| Article Title: | Prospective multicenter validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer: The PROPHECY study |
| Abstract: | PURPOSE Androgen receptor splice variant 7 (AR-V7) results in a truncated receptor, which leads to ligandindependent 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, prospectiveblinded 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. © 2019 American Society of Clinical Oncology. All rights reserved. |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 37 |
| Issue: | 13 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2019-05-01 |
| Start Page: | 1120 |
| End Page: | 1129 |
| Language: | English |
| DOI: | 10.1200/jco.18.01731 |
| PUBMED: | 30865549 |
| PROVIDER: | scopus |
| PMCID: | PMC6494355 |
| DOI/URL: | |
| Notes: | Conference Paper -- Export Date: 3 June 2019 -- Source: Scopus |
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