A blood test that examines circulating tumor cells for the presence of the AR-V7 protein could help determine if a patient with advanced prostate cancer would fare better with chemotherapy or hormone therapy, according to researchers.
Their study, “Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer,” was published in the journal JAMA Oncology.
Medicines that target the androgen receptor, like Zytiga (enzalutamide) and Xtandi (abiraterone), are widely used for the treatment of advanced prostate cancer. But as happens with many medications, tumors often develop a resistance to such therapies.
In some cases, resistance develops when cells produce a variant of the androgen receptor, called AR-V7, that lacks the domain targeted by current androgen receptor inhibitors.
When a patient is first diagnosed with metastatic castration-resistance prostate cancer (MCRPC), the preferred treatment involves androgen receptor inhibitors. But if a patient fails a first-line treatment with these inhibitors, there is no guarantee he’ll respond to a second inhibitor.
In such cases, researchers need biomarkers that help them select which patients should receive a second androgen receptor inhibitor, and which should switch to chemotherapy.
An international team of researchers tested whether AR-V7, measured by a blood test in circulating tumor cells — cells that are shed from the primary tumor and entered the bloodstream — could predict the best treatment approach for each patient.
“The study focused on a critical decision point when patients and their oncologists are choosing what therapy to pursue next,” Alison Allan, PhD, at Western University’s Schulich School of Medicine & Dentistry in Ontario, Canada, and an author of the study, said in a press release.
“We are addressing a critical unmet need by validating that a blood test or liquid biopsy can be used to select a therapy most likely to extend a patient’s life,” Allan said.
The study recruited 142 patients with metastatic castration-resistant prostate cancer from three institutions: London Regional Cancer Program at London Health Sciences Centre (LHSC) in Ontario, Canada; Memorial Sloan Kettering Cancer Center in New York City; and The Royal Marsden National Health Service Foundation Trust in London, England.
All patients had been treated with androgen receptor inhibitors without success. Seventy patients were then moved to another round of treatment with an androgen receptor inhibitor, while 72 patients were treated with taxane-based chemotherapy — Taxotere (docetaxel) or Jevtana (cabazitaxel).
Patients were followed for up to 4.3 years.
As expected, researchers found that patients who were negative for AR-V7 survived significantly longer with an androgen receptor inhibitor (19.8 months) than with chemotherapy (12.8 months).
Conversely, chemotherapy was a better approach for patients who were positive for AR-V7, nearly doubling survival times compared to the androgen receptor inhibitor — 14.3 vs. 7.3 months.
This difference, however, did not reach statistical significance, most likely due to the small number of patients, researchers wrote.
“ARS inhibitors are the preferred first line of treatment because they target the hormones that provide the fuel for prostate cancer cells to grow,” Allan said. “However, at some point, cancer cells can figure out a way to survive without this fuel and become resistant to ARS inhibitors, in many cases through production of the AR-V7 protein. That’s why chemotherapy is sometimes used [as a second-line] therapy.”
Overall, these results suggest that assessing AR-V7 levels in circulating tumor cells through a blood test may help identify the best second-line therapy for patients with metastatic castration-resistant prostate cancer.
Researchers hope that this or similar tests will be used in future practice to tailor treatments and increase a patient’s survival chances. They also plan to collaborate with Epic Sciences to develop similar tests for other cancer types.