ASCO GU: Review of data presented in mCRPC

Dr Kurt Miller – University of Berlin, Germany

Can you give an overview on the latest data being presented on mCRPC at ASCO GU?

Well there are indeed a lot of new drugs coming up. We haven’t seen much change in metastatic castration resistant prostate cancer for a couple of years and now, all of a sudden, we have so many drugs coming up, two of them being enzalutamide, and this is the AFFIRM study, and the other is abiraterone and this is Cougar 301 and Cougar 302 studies.

I had a presentation here on the quality of life data in the AFFIRM study which showed that enzalutamide, which was compared against placebo, delays significantly the deterioration of quality of life in these patients.

How important is the quality of life data from these latest studies?

Besides prolongation of life it’s the most important issue in these patients. Basically, these patients cannot be cured and quality of life is number one or number two on the list in these patients.

How would you describe the challenge for clinicians treating patients with mCRPC?

In the past they didn’t know what to do, now they don’t know what to choose from. No, it’s a little bit of an exaggeration but with these new drugs they need to decide upon the sequence; they need to decide when to stop the drug; they need to decide upon response criteria; they need to decide upon progression criteria, which is not so easy.

Can you give an overview of the AFFIRM and COU-AA-301 and 302?

Well, the basic data from the AFFIRM study were that enzalutamide prolongs life in the region of five months against placebo in these patients and these were post-chemotherapy patients, so pretty late stage. Cougar 301 was the same trial in post-chemo, also abiraterone prolonged life, and then Cougar 302 was the trial where abiraterone was given pre-chemo and it also showed that it prolongs life. So currently we’re in a situation where abiraterone is approved in the US and in Europe in the pre-chemo setting and then we have the ‘old’ docetaxel and then we have enzalutamide approved in the US already for the post-chemo setting. Then it’s expected that it will be approved in Europe during this year in summer or autumn.

Could you describe the differences between enzalutamide and abiraterone?

It’s a different mechanism of action; abiraterone is what we call a CYP17 inhibitor and it basically blocks the production of testosterone within the tumour cell. Enzalutamide, on the other hand, is an AR, androgen receptor, blocker so it blocks testosterone or it blocks the androgen receptor from testosterone. So theoretically you could combine both because of their different mode of action. Currently we have no comparison between the two. Abiraterone must be used together with prednisone because it blocks the adrenal glands; this is not the case for enzalutamide. Both drugs have a very good side effect profile.

What is your advice to clinicians when treating patients with mCRPC?

Right now it’s not too difficult because the agents have different labels. So, as I said, abiraterone is now approved in the pre-chemo setting so everybody probably uses it in this setting and enzalutamide is approved in the post-chemo setting. It’s going to be more difficult within the next two or three years; there’s another trial coming up, the PREVAIL trial, which is the pre-chemo enzalutamide trial and once we have the results then it’s going to be a little bit more difficult in the pre-chemo setting. Do we first use abiraterone or first use enzalutamide? Currently doctors have their sequence.

What are the results on quality of life in the COU-AA-301 study?

It’s not been exactly the same so it’s also always difficult to have a cross-study comparison, but yes, there’s also effects, positive effects, on quality of life in the Cougar studies.

Is there a downside of using either of these agents?

Well in my mind there’s only one downside, that is the effect is limited in terms of time. And all patients do get resistance after some time so this is not the end of the story.

What are the next steps with these agents?

That’s hard to say, there are other drugs coming up, there are other sequences but so far in metastatic castration resistant prostate cancer there is no cure in sight, as with most metastatic solid tumours is the case. So we need to get more information, more knowledge about the principle, how these tumours work, before we get more steps forward.

What are your opinions on combining enzalutamide and abiraterone?

Well, that’s always the question – should we combine, should we sequence it? We would need studies to prove that combining is better than sequencing.

What is your take home message for clinicians from ASCO GU?

These news are not completely new, in a way, but we’re quite happy that we have these new agents available right now because, as I said, in the past, and it’s not too long ago, we had basically only chemotherapy or nothing. So we can now much better serve the patient, that’s the best news you can have.