ASCO GU 2013

Enzalutamide monotherapy: Phase II study results in patients with hormone-naïve prostate cancer

Dr Bertrand Tombal – Catholic University of Louvain, Belgium

There is a lot of activity finding drugs that are active in castration resistant prostate cancer patients but that is targeting 10-15% of the patients who do really badly. We know there are a lot of patients who need androgen deprivation therapy but together with external beam radiation therapy for a short period of time or so. In these patients one of the challenges is to reduce toxicity. So, as you know, in Europe we’ve been using androgen monotherapy, bicalutamide 150, and these drugs have the ability to control the cancer without requiring androgen deprivation therapy, so developing an alternative to standard hormone therapy. These are the preliminary data.

What were the results using enzalutamide?

If I want to make it in a nutshell it would be like a much more achieved anti-androgen than bicalutamide. Bicalutamide blocked the binding to the androgen receptor, this one does the same plus block the translocation in the nucleus and the binding to the androgen responsive element. So basically it is a much more potent anti-androgen so this is why we wanted to use it alone to see what it does. We gave it to patients who need hormone therapy but not together with hormone therapy. We gave it alone, we monitored tumour response using PSA and side effects using a whole battery of tests and here we showed that in terms of PSA response it is working very well. PSA drops very low in most of these patients. We took a very conservative approach of showing a PSA drop of more than 80% to be sure at least that if it didn’t reach that endpoint we know we couldn’t go further. But in fact it does much better than that and it depresses PSA very, very profoundly. So we know, at least initially, it works.

What are the preliminary clinical implications coming out of this study?

Anti-androgen monotherapy is not an unfinished business. There are promises, maybe, for the patient in a few years’ perspective to have a drug that could do the same as androgen deprivation but be without its side effects which, for many patients, is something they expect, I guess.

What are the messages directly for cancer doctors at this point?

Look at these drugs and try to think out of the box of standard hormonal therapy.