The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) aims to bring together all of the different professional disciplines and groups involved in researching and treating urogenital cancers. By bringing together international collaborations of multidisciplinary teams, ANZUP can perform clinical trials that directly improve patient outcomes.
In Australia, prostate cancer is the most commonly diagnosed cancer in men. Because the cancer reacts to testosterone, standard treatment for this is testosterone suppression. By lowering the level of testosterone medically, the cancer will stabilise and sometimes regress. While most men will recover, treatment has remained largely unchanged for 70 years—posing the question: ‘can we improve survival rates even further?’
If cancer is localised to the prostate it can usually be cured with radiation and therapy, but if it progresses it’s usually not curable, but can be managed with hormonal therapy. As the results are varied, some men will respond to treatment and the cancer will never progress—those men will likely die of something else. However, for other men it does progress and cause significant problems. Once it has progressed and spread, patients are much more likely to die of the cancer, especially if they are younger and otherwise healthy—it’s a major cause of cancer death because the type of cancer is so common.
The ENZAMET trial
The ENZAMET trial, led by ANZUP, looks at men with newly diagnosed metastatic prostate cancer—prostate cancer that has spread throughout the body. This trial uses the drug enzalutamide which blocks signalling testosterone in the cells. This drug is already approved for use in cases where men have prostate cancer that has progressed despite hormone therapy and in that situation, it prolongs survival.
ANZUP Chair and Head of Monash University’s Eastern Health Clinical School, Professor Ian Davis, talks about the drug being used as an earlier treatment.
“This is a very simple question: alright, it already works later down the track, so why don’t we bring it in earlier and see if that makes a difference?” said Prof Davis.
Patients enrolled in the ENZAMET trial received standard hormonal therapy (androgen deprivation), and half received enzalutamide while the other half received the older standard drug. So far this is the only trial that has used those two treatments together.
Results from the ENZAMET trial showed a 33% reduction in hazard ratio for death from prostate cancer. The overall improvement at the three year mark was eight percent in those who received enzalutamide.
“That is particularly impressive because the men who didn’t get the drug in the trial still were able to access the drug later on, and many did. So basically, this trial shows that the drug works even more powerfully when administered early on.
“We want to do research that will lead to changes in routine practice, we don’t want to do something just for the sake of scientific curiosity but that won’t go any further,” said Prof Davis.
The ENZAMET trial has already impacted clinical practice in the USA and Europe, with the FDA approving enzalutamide for use in this setting in December 2019.
When analysing data, ANZUP looked at more than just survival rates—the clinicians wanted to find out about quality of life outcomes. All cancer treatments have side effects, but ENZAMET was able to show that even with the side-effects of standard therapy and enzalutamide, overall quality of life was measurably improved.
Where to from here?
“Well, we’ll be aiming for a clean sweep at the ACTA Trial of the Year Awards,” joked Prof Davis.
The trial will continue to give value. ANZUP plans to publish many other papers based on the trial, while the group begins laboratory work to complement the study. The quality of life and health economics information will be publicly released soon.
“We’ve also got the health economics information coming soon which will be interesting and important when it comes to looking at getting it approved in Australia. We’ll be looking at ‘what does it cost, and what are we saving by using a drug that’s more expensive than other therapies but makes people live longer’,?” asked Prof Davis.