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Expression of AR-V7 and ARv in Circulating Tumor Cells Correlates with Outcomes to Taxane Therapy in Men with Metastatic Prostate Cancer Treated in TAXYNERGY.

TitleExpression of AR-V7 and ARv in Circulating Tumor Cells Correlates with Outcomes to Taxane Therapy in Men with Metastatic Prostate Cancer Treated in TAXYNERGY.
Publication TypeJournal Article
Year of Publication2019
AuthorsTagawa ST, Antonarakis ES, Gjyrezi A, Galletti G, Kim S, Worroll D, Stewart J, Zaher A, Szatrowski TP, Ballman KV, Kita K, Tasaki S, Bai Y, Portella L, Kirby BJ, Saad F, Eisenberger MA, Nanus DM, Giannakakou P
JournalClin Cancer Res
Volume25
Issue6
Pagination1880-1888
Date Published2019 Mar 15
ISSN1078-0432
Abstract

PURPOSE: Biomarkers aiding treatment optimization in metastatic castration-resistant prostate cancer (mCRPC) are scarce. The presence or absence of androgen receptor (AR) splice variants, AR-V7 and AR, in mCRPC patient circulating tumor cells (CTC) may be associated with taxane treatment outcomes. A novel digital droplet PCR (ddPCR) assay assessed AR-splice variant expression in CTCs from patients receiving docetaxel or cabazitaxel in TAXYNERGY (NCT01718353). Patient outcomes were examined according to AR-splice variant expression, including prostate-specific antigen (PSA) response and progression-free survival (PFS).

RESULTS: Of the 54 evaluable patients, 36 (67%) were AR-V7, 42 (78%) were AR, 29 (54%) were double positive, and 5 (9%) were double negative. PSA response rates at any time were numerically higher for AR-V7 versus AR-V7 (78% vs. 58%; = 0.23) and for AR versus AR (92% vs. 57%; = 0.04) patients. When AR-V mRNA status was correlated with change in nuclear AR from cycle 1 day 1 to day 8 ( = 24), AR-V7 patients ( = 16) had a 0.4% decrease versus a 12.9% and 26.7% decrease in AR-V7/AR ( = 3) and AR-V7/AR ( = 5) patients, respectively, suggesting a dominant role for AR-V7 over AR. Median PFS was 12.02 versus 8.48 months for AR-V7 versus AR-V7 (HR = 0.38; = 0.01), and 12.71 versus 7.29 months for AR versus AR (HR = 0.37; = 0.02). For AR-V7, AR-V7/AR, and AR-V7/AR patients, median PFS was 8.48, 11.17, and 16.62 months, respectively ( = 0.0013 for trend).

CONCLUSIONS: Although detection of both CTC-specific AR-V7 and AR by ddPCR influenced taxane outcomes, AR-V7 primarily mediated the prognostic impact. The absence of both variants was associated with the best response and PFS with taxane treatment.See related commentary by Dehm et al., p. 1696.

DOI10.1158/1078-0432.CCR-18-0320
Alternate JournalClin. Cancer Res.
PubMed ID30301829
PubMed Central IDPMC6432911
Grant ListR21 CA216800 / CA / NCI NIH HHS / United States
T32 CA062948 / CA / NCI NIH HHS / United States
T32 CA203702 / CA / NCI NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States
Division: 
Biostatistics
Category: 
Faculty Publication