Test Predicts Benefit of Targeted Cancer Treatments

There is an urgent need to develop biomarker strategies to a priori identify castration-resistant prostate cancer (CRPC) patients who will derive minimal benefit from androgen receptor (AR) targeting and offer them an alternative treatment paradigm.

The androgen receptor is known to play an important role in helping cancers to become resistant to treatment with abiraterone and enzalutamide, which are standard treatments for men whose cancer is resistant to traditional hormone blocking therapy and has spread round the body.

A large international team of scientists collaborating with those at the Institute of Cancer Research analyzed blood samples from 265 men with advanced prostate cancer who were being treated with abiraterone or enzalutamide, either before or after docetaxel chemotherapy. In two cohorts, patients were required to have histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation, progressive disease despite ‘castration levels’ of serum testosterone of less than 50 ng/dL.

Serum prostate-specific antigen (PSA) was assessed within one week of starting treatment and monthly thereafter. Circulating DNA was extracted from one to two mL of plasma with the QIAamp Circulating Nucleic Acid Kit. Rare mutation detection assays were performed for the AR mutations. Emulsified polymerase chain reaction (PCR) reactions were run on a Mastercycler Nexus GSX1 and Droplet Digital PCR samples were read on a Bio-Rad QX200 droplet reader.

In the primary trial of 171 patients, men in whom a blood test detected multiple copies of the gene that carries the instructions for making the androgen receptor were four times more likely to die over the course of the study than those who did not. The study included both patients who had previously received chemotherapy and those who did not. The findings were confirmed in a second group of 94 patients where men with multiple copies had an eight-fold shorter response to treatment than men with one or two copies of the gene.

Gerhardt Attard, MD, PhD, a clinical scientist and team leader of the study said, “We have developed a robust test that can be used in the clinic to pick out which men with advanced prostate cancer are likely to respond to abiraterone and enzalutamide, and which men might need alternative treatments. Our method costs less than GBP 50, is quick to provide results, and can be implemented in hospital laboratories.” The study was published on May 3, 2017, in the journal Annals of Oncology.