Variant Makes Chemotherapy Preferred Option for Some Advanced Prostate Cancer Patients

Men with AR-V7 variant more likely to be resistant to hormone drugs.

For patients with advanced prostate cancer who possess a specific variant, the best treatment option may be chemotherapy.

In a study published online in JAMA Oncology, researchers from Johns Hopkins' Kimmel Cancer Center and James Buchanan Brady Urological Institute found advanced prostate cancer patients with the androgen receptor splice variant-7 (AR-V7) respond to chemotherapy similarly to men lacking the variant. Patients who carry this variant are more likely to be resistant to hormone drugs commonly used in treatment of the disease.

"Our study shows that men who have the AR-V7 gene variant and usually don't respond to either abiraterone or enzalutamide, are not at a disadvantage when given chemotherapy drugs," said Kimmel Cancer Center oncologist Emmanuel Antonarakis, MD, in a press release.

Prior research has shown that patients with the AR-V7 variant are resistant to hormonal drugs, such as enzalutamide or abiraterone, which treat castration-resistant prostate cancer.

For the current trial, among 37 patients treated with either of the chemotherapy drugs docetaxel or cabazitaxel, 17 had detectable AR-V7 variant in their blood. A comparison of men with and without the gene variant did not show a statistical difference in declining PSA levels, the timeframe for cancer progression, or overall survival.

The results showed that 7 of 17 men in the trial with the AR-V7 variant treated with chemotherapy achieved a 50% decrease in their prostate-specific antigen (PSA) level.

The results also showed that patients who were AR-V7-positive at the start of chemotherapy became AR-V7-negative during the course of therapy. While the clinical significance of this finding is undetermined, the researchers hypothesized that some of these patients may become re-sensitized to enzalutamide or abiraterone.

There are currently no commercially available tests for AR-V7 yet, but the researchers plan to develop and an AR-V7 test that could be used more widely.

"The ultimate goal is to address needs of patients who are failing standard therapy," researcher Jun Luo, PhD said in a press release. "By using the biomarker to improve patient-doctor decision-making, we could realize a therapeutic benefit without having to find a new drug."