HOXB13 is an androgen receptor (AR) co-regulator 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.
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).
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 while 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%).
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2024 Jan 18 [Epub ahead of print]
Susan Halabi, Siyuan Guo, Joseph J Park, David M Nanus, Daniel J George, Emmanuel S Antonarakis, Daniel Costin Danila, Russell Zelig Szmulewitz, Donald P McDonnell, John D Norris, Changxue Lu, Jun Luo, Andrew J Armstrong
Duke Medical Center, Durham, NC, United States., Duke University School of Medicine, Durham, United States., Weill Cornell Medicine, New York, NY, United States., Duke University School of Medicine, Durham, NC, United States., University of Minnesota, Minneapolis, United States., Memorial Sloan Kettering Cancer Center, New York, NY, United States., University of Chicago, Chicago, IL, United States., Duke University School of Medicine, Durham, North Carolina, United States., Johns Hopkins University School of Medicine, Baltimore, MD, United States., Johns Hopkins University School of Medicine, Baltimore, MARYLAND, United States.