New results for prostate cancer drug abiraterone

Abiraterone is showing promise in early-stage trials

• Please note – Abiraterone has now been approved by NICE. 

Last July we blogged about exciting early trial results for abiraterone, a drug for treating aggressive prostate cancer – a disease that claims around 10,000 lives every year in the UK.  A small study of just 21 men showed that abiraterone seemed to shrink tumours in up to 80 per cent of the patients on the trial.

Now scientists have published results from a larger trial, and the good news is that abiraterone still looks promising as a treatment for prostate cancer.

Cancer Research UK is particularly excited about the progress of abiraterone, as we played an important role in the early development and testing of the drug.  We funded the lead researchers on this current study, and we are also currently funding an early-stage clinical trial of abiraterone for women with advanced breast cancer.

Please note that there are no trials of abiraterone for prostate cancer that are currently recruiting patients.

Let’s take a look at the story in more detail.

The new results

Researchers at the Institute of Cancer Research and The Royal Marsden Hospital tested the drug on 54 men with aggressive, advanced prostate cancer. In most cases, the cancer had spread around the body, causing many of them discomfort and pain.

The men were given abiraterone daily and, twelve weeks later, were given a PSA test and a CT scan to see if the drug had worked.

The scientists found that abiraterone worked for around two-thirds of the men on the trial, lowering their PSA levels, causing the tumours to shrink and relieving pain. It wasn’t a permanent cure, as the effects only lasted an average of 8 months.  But, interestingly, for men who carried a faulty version of a gene called ERG, the effects lasted much longer – up to 18 months.

This may not sound like long, but it’s certainly a significant improvement on what might be expected for men with such advanced cancer.

What’s the science behind it?

Abiraterone is an interesting drug because it works in a different way to existing prostate cancer treatments.  The male sex hormone testosterone drives the growth of most prostate cancers, so men are often given drugs that block the production of this hormone in their testicles. This is known as hormone therapy, and while it’s often very successful in the short-term, it isn’t perfect.

In many cases, the cancer starts to grow again after a few months or even years. Such cancers are called hormone-resistant (or hormone-refractory) prostate cancers. This happens because cancer cells evolve to cope with a lower level of testosterone, and also because small amounts of testosterone are produced in other parts of the body besides the testicles.

Abiraterone was designed to block the actions of a protein called CYP17, which is involved in making testosterone.  Unlike current hormone treatments, it stops production of testosterone all over the body, as well as in the testicles. This deprives prostate cancer cells of the testosterone ‘signal’ telling them to grow and divide.

Importantly, the results of these early abiraterone trials tell us that aggressive hormone-resistant prostate cancer is still a disease driven by testosterone. So further research into drugs that block the production or actions of testosterone throughout the body are likely to lead to even better ways to treat this disease in the future.

Getting personal

Another interesting aspect of the research is the discovery that men carrying a specific gene fault are more likely to respond to abiraterone for longer.  We’ve already blogged about how genetic research is helping doctors to improve treatment for other cancers – such as breast cancer – and this looks like being another good example.

In research published recently, the same team of scientists  purified ‘escapee’ prostate cancer cells from the blood of 89 patients involved in the early-stage abiraterone trials.  The team were investigating the ERG gene, which is often overactive in aggressive prostate cancers.

Normally, the activity levels of ERG are tightly controlled, as it sends a powerful signal that tells cells divide.  But in many prostate cancers, the DNA near the gene gets broken, and ERG is relocated next to another gene called TMPRSS2, whose activity is controlled by testosterone.

This relocation effectively means that ERG becomes controlled by testosterone, explaining why this hormone can fuel the growth of prostate cancers.  (As an aside, we blogged about this gene fault last year, when researchers discovered that the relocated ERG gene can also be activated by oestrogen).

In their research, the scientists found that men whose tumours showed this rearrangement of ERG were more likely to respond well to treatment with abiraterone (although just over a third of them did not show a significant response).  Although this intriguing finding needs to be backed up by larger studies, it could lead to future tests allowing doctors to tailor treatment to suit an individual’s cancer.

What next?

These new results are impressive, and provide hope for treatment of prostate cancer in the future.  But it’s important to stress that abiraterone is still some way from being a treatment that can routinely be given to patients.  We currently only have results from small trials, and we need more data before we can be sure that it is safe and effective for general use.

Abiraterone is currently being tested in a large-scale trial, which recently finished recruiting around 1,150 patients at 150 hospitals worldwide.  It’s important to stress that this trial is now closed – there are no current trials of abiraterone for prostate cancer that are actively recruiting patients.

If the results of the trial are positive – and if the drug clears the appropriate regulatory hurdles – then we could see if coming into general use as early as 2011, although this is certainly not a date set in stone.

The story of abiraterone highlights the importance of scientists and doctors working together with medical research charities and the pharmaceutical industry (the drug’s patent is owned by Cougar Biotechnology, who have just been bought out by Johnson & Johnson). It’s great to see positive results coming after years of hard work, and we look forward to seeing the results of the larger-scale trials.

Kat

There’s a handy Q&A section on abiraterone on our CancerHelp UK website if you’d like to know more.

If you have prostate cancer and would like more information about the disease, please visit CancerHelp UK , or contact our Cancer Information nurses.

References:

Attard, G. et al (2009). Selective Inhibition of CYP17 With Abiraterone Acetate Is Highly Active in the Treatment of Castration-Resistant Prostate Cancer Journal of Clinical Oncology DOI: 10.1200/JCO.2008.20.0642

Attard, G. et al (2009). Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer Cancer Research, 69 (7), 2912-2918 DOI: 10.1158/0008-5472.CAN-08-3667