Blood Tests May Identify Patients Less Likely to Benefit from Hormone Therapies

Blood Tests May Identify Patients Less Likely to Benefit from Hormone Therapies

Two new blood tests that detect a variant of the androgen receptor — a protein that binds male hormones called androgens — may help to predict those advanced prostate cancer patients who would not benefit from anti-androgen therapies, new research suggests.

The tests, which are called “liquid biopsies,” may help guide care toward more effective treatments.

The research, “The PROPHECY trial: Multicenter prospective trial of circulating tumor cell (CTC) AR-V7 detection in men with mCRPC receiving abiraterone (A) or enzalutamide (E),” was recently presented at the 2018 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

A variation of the androgen receptor, called AR-V7, has been linked to poor responses to drugs like Zytiga (enzalutamide) and Xtandi (abiraterone) in patients with castration-resistant prostate cancer.  This happens because the medicines target a domain of the receptor that is missing in the AR-V7 version. (Castration resistant means the disease progresses despite androgen depletion therapy.)

Researchers have developed tests that detect AR-V7 in tumor circulating cells — cells that shed from the tumor or metastasis into circulation – but whether these could be used to predict the effectiveness of Zytiga and Xtandi in metastatic castration-resistant prostate cancer is unclear.

Investigators at the Duke Cancer Institute designed a multi-center study — called PROPHECY (NCT02269982) — to evaluate how well the blood tests predict the effectiveness of these hormone therapies.

A total of 118 men were enrolled at five medical centers to provide external validation for the two tests. One is marketed by Epic Sciences and Genomic Health and is called AR-V7 CTC nuclear protein test, while the other was developed at Johns Hopkins University and is called CTC AR-V7 RNA test.

Besides examining the two AR-V7 CTC tests, the scientists also assessed additional genomic alterations that may help improve treatment selection and study the development of drug resistance.

“We have therapies to treat recurrent, metastatic prostate cancer, but they don’t work on everyone, and cross-resistance is a major emerging problem in our field. It’s important to know who will be more likely to respond and who has little chance of benefiting in order to rapidly provide alternative, more effective therapies or to develop new therapies for these men,” Andrew Armstrong, MD, associate director for clinical research in the Duke Prostate and Urologic Cancer Center, said in a press release.

For both tests, AR-V7 detection correlated with worse progression-free survival (PFS) — the length of time during or after treatment without disease progression — and overall survival (OS). While the Johns Hopkins test appeared to be more sensitive and flagged more non-responding patients, the Epic test seemed to be more specific, leading to no false-positive data.

“We validate AR-V7 detection as an independent (…) predictive biomarker of short PFS and OS,” the scientists wrote.

“Having this predictive power could spare many men from undergoing therapies that would simply not benefit them, saving time, money and a great deal of emotional distress,” Armstrong said. “The results of this study are clinically useful in guiding care, particularly in men with high-risk disease and those who have already tried enzalutamide or abiraterone.”

Patients with advanced, hormone-resistant prostate cancer typically require treatment with either Zytiga or Xtandi, or alternatives such as chemotherapy. The blood tests could help guide care for these patients, as they provide results in just a few days, according to scientists.

Investigators are now evaluating similar tests to better identify patients with AR-V7-negative and -positive disease who could benefit from new treatments.

These patients, Armstrong said, could be started on chemotherapy or be included in clinical trials for other types of treatment, including immunotherapy, or targeted therapies. “This represents a major step forward in the care of men with aggressive prostate cancer,” he added.