Using a blood-based test to personalise treatment for advanced prostate cancer

Professor Attard plans to recruit men with advanced hormone resistant prostate cancer to a clinical trial called PARADIGM. The trial will be national with several centres in the UK recruiting patients. The overall aim of this trial is to determine whether doctors and clinicians can use a simple blood test to determine the treatment that’s most likely to work.

Once they’ve decided to join the trial, men will have a blood test, and Professor Attard and his team will extract the tumour material (DNA) from blood and test it for changes in the gene that instructs the Androgen Receptor, a key driver of prostate cancer growth.

In a previous project funded by Prostate Cancer UK and The Movember Foundation, Professor Attard showed that men whose prostate cancers had specific changes in the Androgen Receptor gene were likely to be resistant to treatments like abiraterone and enzalutamide. This genetic change could be detected in the tumour DNA extracted from blood several months before the man started feeling symptoms of his cancer worsening.

In the PARADIGM trial, Professor Attard will follow up on this work, as well as other data suggesting that although men with these Androgen Receptor gene mutations may be resistant to abiraterone or enzalutamide, they might in fact respond better than expected to docetaxel or cabazitaxel chemotherapy.

Professor Attard and his team will now use his liquid biopsy test for Androgen Receptor changes on men who haven’t already started treatment. They’ll divide men into those with Androgen Receptor changes and those without. Those without the change will continue to be treated as they, and their clinician, think best. Those with the change will be randomly assigned to treatment with either additional hormone therapies like abiraterone / enzalutamide or docetaxel / cabazitaxel chemotherapy.

This trial will first seek to confirm that second-line hormone therapies don’t work well for men with changes to the Androgen Receptor. It will also determine if these same men will actually do much better with chemotherapy instead. Finally, the PARADIGM trial will clearly demonstrate whether testing men for changes to the Androgen Receptor gene as soon as their cancer becomes hormone resistant, then offering them treatment based on the result of that test, would mean that men get access to the medication most likely to work for them the first time round.

If this is successful, Professor Attard hopes that by the end of the trial they will have collected all the scientific data necessary to persuade health regulators to make this test available to all men with hormone resistant prostate cancer, so that doctors can work out which treatment route would be most beneficial for them.

Grant information

Reference - MA-TR15-007
Researcher - 
Professor Gert Attard
Institution - University College London
Award - £859,367.00