AR-V7 Biomarker Could Guide Treatment in mCRPC Patients

In men with metastatic castration-resistant prostate cancer (mCRPC), the presence of androgen receptor V7 (AR-V7) in circulating tumor cells did not significantly affect response to treatment with taxane therapy, according to the results of a small prospective study (Abstract 138) presented at a press conference held in advance of the 2015 ASCO Genitourinary Cancers Symposium.

In fact, researchers led by Emmanuel Antonarakis, MD, assistant professor of oncology and urology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, found that men who had AR-V7 detected in circulating tumor cells (AR-V7–positive) may retain their sensitivity to taxane-based treatment.

An earlier study by Antonarakis and colleagues found that AR-V7–positive mCRPC patients treated with either enzalutamide or abiraterone fared worse than AR-V7–negative patients.

AR-V7 is a truncated form of the androgen receptor that is detected in about one-third of patients with CRPC. AR-V7 lacks the ligand-binding domain of the androgen receptor, the target of enzalutamide and abiraterone.

“AR-V7 may potentially serve as a treatment selection marker in men with mCRPC seeking therapy with either taxanes or enzalutamide/abiraterone,” Antonarakis said. “Before the data are clinically actionable, we need to prospectively validate these findings in at least one multi-setting clinical trial.”

In this small study, the researchers hypothesized that men who were AR-V7–positive may retain sensitivity to taxanes. To explore this idea they enrolled 37 patients with mCRPC who had been scheduled to start chemotherapy with docetaxel or cabazitaxel, and used a quantitative reverse transcription polymerase chain reaction assay to determine if they were AR-V7–positive (17 patients; 45.9%) or AR-V7–negative.

Data from the analysis showed that AR-V7 status did not seem to affect treatment response in patients treated with taxanes, with similar outcomes seen in AR-V7–positive and AR-V7–negative patients for median prostate-specific antigen (PSA) progression-free survival (4.5 months vs 6.2 months; hazard ratio [HR] = 1.72; P = .32) and median progression-free survival (5.1 months vs 6.9 months; HR = 2.65; P = .11).

The researchers then compared outcomes from this study with that of the 62 patients treated with enzalutamide/abiraterone from their previous study. This analysis showed that men who were AR-V7–positive had better outcomes when treated with taxanes compared with enzalutamide/abiraterone.

“What is notable here is in positive patients there was a 41% PSA response, which should be compared with 0% with AR-V7 patients receiving enzalutamide or abiraterone,” Antonarakis said. Patients who were AR-V7–positive also had longer median PSA progression-free survival and progression-free survival.

In providing an example, Antonarakis said that if a patient is AR-V7–positive, they would have a greater chance of clinical or radiographic progression with enzalutamide or abiraterone compared with a taxane (HR = 0.21). “Meaning that if a patient is AR-V7–positive, the chance of progression on a taxane is approximately 79% lower than if they receive AR-directed therapy,” he said.

Antonarakis noted that there is no commercially available assay for AR-V7 at this time.