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.
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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.
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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.
Reference
- 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]
