ASCO 2012: Advances in metastatic castration-resistant prostate cancer with abiraterone

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Published: 12 Jun 2012
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Dr Karim Fizazi - Institut Gustave Roussy, France; Dr Oscar Goodman - Nevada Cancer Institute, USA

Dr Karim Fizazi from Institut Gustave Roussy, Paris, France, talks to Dr Oscar Goodman from the UC San Diego Nevada Cancer Institute in Las Vegas, USA, on new data presented at ASCO 2012 on abiraterone in metastatic castration-resistant prostate cancer (mCRPC).

 

Dr Goodman reminds the viewers of the COU-AA-301 study comparing abiraterone vs. prednisone post-doxetaxel in mCRPC.  He then outlines the new post-hoc analysis of this study looking at the amount of doxetaxel received prior to abiraterone therapy, the interval between completion of doxetaxel and initiation of abiraterone, and the reason for discontinuation of doxetaxel. 

 

Dr Goodman comments on the new finding from this post-hoc analysis that highlights the importance of drug administration timing in disease management, and notes the hope that this study offers to patients to move this cancer from deadly to a chronic disease.

 

This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company).

ASCO 2012, Chicago, USA

Advances in metastatic castration-resistant prostate cancer with abiraterone

Dr Oscar Goodman – Nevada Cancer Institute, USA interviewed by Dr Karim Fizazi – Institut Gustave Roussy, France



Hello everybody, I’m Karim Fizazi from Gustave Roussy Institut in Villejuif, France. I’m here in Chicago at the ASCO meeting and I have the pleasure to have with me Dr Oscar Goodman from the National Cancer Institute in Las Vegas. Dr Goodman is going to present some new data at the ASCO meeting and I’m happy to ask him a couple of questions about that. So first, Dr Goodman, can you remind us how abiraterone works, what it is exactly?

Abiraterone acetate works by inhibiting all male hormone synthesis, androgen synthesis, both within the adrenal gland as well as within the cancer cells themselves. So basically it’s optimal hormonal therapy.

And the COU-301 trial which was basically the first phase III trial to explore the efficacy of abiraterone acetate was conducted in advanced disease. Can you summarise the trial?

Yes, this study was a study of 1,200 patients with metastatic prostate cancer that was castrate resistant, that had progressed after docetaxel-based chemotherapy. Men were randomised to receive the abiraterone acetate and prednisone versus a placebo and prednisone. The randomisation was done in a 2 to 1 fashion favouring the abiraterone.

Can you summarise the main results of the trial?

The main result of the trial was that abiraterone acetate has a substantial survival benefit. It was the first therapy that was hormonally based that was found to have a survival benefit following docetaxel. What we have done now is done a post hoc analysis on this study basically looking at three different things. One is how much docetaxel was delivered to the patient prior to starting abiraterone; number two is the interval between completion of the docetaxel and the initiation of the abiraterone and number three is the reason for discontinuation of the docetaxel, either related to disease progression or to other causes.

And what did you find?

We found that the survival benefit was preserved regardless of what any of those three indications were. Interestingly though, we also looked at intra-treatment groups so, for instance, patients who received abiraterone acetate. We looked at the three variables that I mentioned and what we did find is that patients who received abiraterone acetate that discontinued docetaxel due to progression of disease versus all others had less of a benefit. So that was a new finding and it makes us really think about the timing patients are going to have when they come off of docetaxel and when they start abiraterone. It also makes us think that there could be some potential cross-resistance between the two drugs so clinically using these data you might ask how many cycles of docetaxel would you want to give before starting abiraterone. Typically, we think, about 10-12 cycles is a maximum course but these data make you start re-thinking that and it’s really going to require a lot more work, several studies looking at sequencing and timing. But this opens the door to starting to at least ask the appropriate questions that can be answered using appropriate clinical trials.

I was actually impressed to see the duration of overall survival for these patients when you start the clock from docetaxel to the end, it’s surely now two years plus.

Yes.

And that’s really impressive to me. If you remember ten years ago all the patients were supposed to live just a year or something around that before the docetaxel era.

Eighteen months.

So we’re really making progress.

Yes, we’re looking at the difference now is a whole other year on what we used to have following docetaxel. So we’re making progress. What we’re going to really see over time with these new therapies is a transformation of metastatic castration-resistant prostate cancer from a lethal disease to a chronic disease. And hopefully after that we’ll actually see some cures coming out but these are very important steps and it really hits home the fact that the androgen receptor signalling remains an Achilles’ heel for the tumour.

A key player.

A key player, yes.

Thank you very much Dr Goodman, thanks.

Thank you, Dr Fizazi.