Circulating tumor cell (CTC)-based androgen receptor splice variant-7 (AR-V7) testing was validated as a prognostic test for men with castration-resistant prostate cancer (CRPC) receiving hormone therapy, according to a study published in the Journal of Clinical Oncology.1
Previous studies suggest that AR-V7 is associated with poor outcomes with abiraterone or enzalutamide, but sensitivity to docetaxel or cabazitaxel.
“This expanded analysis confirms the negative prognostic impact of CTC-based AR-V7 detection in patients with CRPC…and suggests that this biomarker panel may be useful in prediction of response to androgen receptor–targeted treatment applied in the first- and second-line settings,” wrote the authors.
The prospective study included 202 men with CRPC receiving abiraterone or enzalutamide. Prior treatment with taxane chemotherapy or alternative hormonal therapy was permitted. Baseline status of CTCs and AR-V7 were analyzed; the relative abundance of AR-V7 was determined by the ratio AR-V7 transcript to AR–full-length transcript.
At baseline, the median age was 70.3, 41.6% had prior hormonal therapy, 29.3% had prior docetaxel, 86.3% had bone metastases, and 28% had visceral metastases, though these characteristics were higher in the CTC-positive/AR-V7-positive group. The median baseline PSA was 13.7, 31.4, and 92.0 ng/dL in the CTC-negative, CTC-positive/AR-V7-negative, and CTC-positive/AR-V7-positive groups, respectively.
The median progression-free survival (PFS) in the overall cohort was significantly longer in the CTC-negative group at 13.9 months (95% CI, 11.0-not reached months) and the CTC-positive/AR-V7-negative group at 7.7 months (95% CI, 6.2-10.1 months) compared with the CTC-positive/AR-V7-positive group at 3.1 months (95% CI, 2.3-3.7 months).
The median overall survival (OS) in the overall cohort was significantly longer in the CTC-negative group at 28.7 months (95% CI, 28.4-not reached months) and the CTC-positive/AR-V7-negative group at 29.5 months (95% CI, 18.4-not reached months) compared with the CTC-positive/AR-V7-positive group at 11.2 months (95% CI, 8.3-17.1 months).
CTC and AR-V7 status remained prognostic for PFS and OS when the cohort was stratified by first- and second-line hormonal therapy, even after multivariable Cox regression analysis.
According to the authors, the results from this study suggest that the CTC-based AR-V7 mRNA assay should be interpreted using the CTC-negative, CTC-positive/AR-V7-negative, and CTC-positive/AR-V7-positive categories. Studies are ongoing to further validate these findings.
- Antonarakis ES, Lu C, Luber B, et al. Clinical significance of androgen receptor splice variant-7 mRNA detection in circulating tumor cells of men with metastatic castration-resistant prostate cancer treated with first- and second-line abiraterone and enzalutamide. J Clin Oncol. 2017 April 6. doi: 10.1200/JCO.2016.70.1961 [Epub ahead of print]