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The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.

Publication ,  Conference
Halabi, S; Guo, S; Park, JJ; Nanus, DM; George, DJ; Antonarakis, ES; Danila, DC; Szmulewitz, RZ; McDonnell, DP; Norris, JD; Lu, C; Luo, J ...
Published in: Clin Cancer Res
March 15, 2024

PURPOSE: HOXB13 is an androgen receptor (AR) coregulator specifically expressed in cells of prostatic lineage. We sought to associate circulating tumor cell (CTC) HOXB13 expression with outcomes in men with mCRPC treated with abiraterone or enzalutamide. EXPERIMENTAL DESIGN: We conducted a retrospective analysis of the multicenter prospective PROPHECY trial of mCRPC men (NCT02269982, n = 118) treated with abiraterone/enzalutamide. CTC detection and HOXB13 complementary DNA (cDNA) expression was measured using a modified Adnatest, grouping patients into 3 categories: CTC 0 (undetectable); CTC+ HOXB13 CTC low (<4 copies); or CTC+ HOXB13 CTC high. The HOXB13 threshold was determined by maximally selected rank statistics for prognostic associations with overall survival (OS) and progression-free survival (PFS). RESULTS: We included 102 men with sufficient CTC HOXB13 cDNA, identifying 25%, 31%, and 44% of patients who were CTC 0, CTC+ HOXB13 low, and CTC+ HOXB13 high, respectively. Median OS were 25.7, 27.8, and 12.1 months whereas the median PFS were 9.0, 7.7, and 3.8 months, respectively. In subgroup analysis among men with CellSearch CTCs ≥5 copies/mL and adjusting for prior abi/enza treatment and Halabi clinical risk score, the multivariate HR for HOXB13 CTC detection was 2.39 (95% CI, 1.06-5.40) for OS and 2.78 (95% CI, 1.38-5.59) for PFS, respectively. Low HOXB13 CTC detection was associated with lower CTC PSA, PSMA, AR-FL, and AR-V7 detection, and more liver/lung metastases (41% vs. 25%). CONCLUSIONS: Higher CTC HOXB13 expression is associated with AR-dependent biomarkers in CTCs and is adversely prognostic in the context of potent AR inhibition in men with mCRPC.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

March 15, 2024

Volume

30

Issue

6

Start / End Page

1152 / 1159

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Receptors, Androgen
  • RNA
  • Prostatic Neoplasms, Castration-Resistant
  • Prospective Studies
  • Phenylthiohydantoin
  • Oncology & Carcinogenesis
  • Nitriles
  • Neoplastic Cells, Circulating
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Halabi, S., Guo, S., Park, J. J., Nanus, D. M., George, D. J., Antonarakis, E. S., … Armstrong, A. J. (2024). The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide. In Clin Cancer Res (Vol. 30, pp. 1152–1159). United States. https://doi.org/10.1158/1078-0432.CCR-23-3017
Halabi, Susan, Siyuan Guo, Joseph J. Park, David M. Nanus, Daniel J. George, Emmanuel S. Antonarakis, Daniel Costin Danila, et al. “The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.” In Clin Cancer Res, 30:1152–59, 2024. https://doi.org/10.1158/1078-0432.CCR-23-3017.
Halabi, Susan, et al. “The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.Clin Cancer Res, vol. 30, no. 6, 2024, pp. 1152–59. Pubmed, doi:10.1158/1078-0432.CCR-23-3017.
Halabi S, Guo S, Park JJ, Nanus DM, George DJ, Antonarakis ES, Danila DC, Szmulewitz RZ, McDonnell DP, Norris JD, Lu C, Luo J, Armstrong AJ. The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide. Clin Cancer Res. 2024. p. 1152–1159.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

March 15, 2024

Volume

30

Issue

6

Start / End Page

1152 / 1159

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Receptors, Androgen
  • RNA
  • Prostatic Neoplasms, Castration-Resistant
  • Prospective Studies
  • Phenylthiohydantoin
  • Oncology & Carcinogenesis
  • Nitriles
  • Neoplastic Cells, Circulating
  • Male