Clinical Newswire

M: Prof Gordon McVie, ecancer
R: Prof Charles J. Ryan, Associate Professor of Medicine and Urology at the University of California San Francisco, USA (UCSF)

M: Prof Charles Ryan from UCSF thank you very much for coming all the way to Madrid and for taking time out to talk to ecancer. You are giving a plenary lecture about the new horizons in management of prostate cancer and it is really quite exciting. You are a professor of medicine and urology?
R: That is correct.
M: Looking from San Francisco, what is your view of prostate cancer management? It is changing quite dramatically just in profile…
R: Absolutely. Well, first of all is a pleasure to be here in Madrid always and to be presenting new data which is interesting and exciting. The management of metastatic castration-resistant prostate cancer has undergone a sea change in the last 5 years. We have five new agents that are available. They have received regulatory approval because they have improved overall survival for patients. What that means is of course survival has never been better, but we now are seeing sequential use of more than one of these therapies. That is on one hand very exciting and important for us in the clinic. For those of us who design and implement clinical trials it creates a few issues in terms of designing trials that can incorporate the potential or the possibility that patients will receive numerous therapies sequentially.
M: Just to be quite clear: These five new agents are approved by the FDA for treatment of metastatic castration-resistant prostate cancer after chemotherapy.
R: Well, it is a mixture.
M: What they all look like?
R: Going back 10 years: we had docetaxel chemotherapy. Then, we had cabazitaxel which is a taxoid chemotherapy approved for post-docetaxel chemotherapy patients. Then, in the US, we had sipuleucel-T, a cellular vaccine, approved that was irrespective of chemotherapy, really. Then, we had abiraterone approved in a post-chemotherapy space than in a pre-chemotherapy space. Then we had enzalutamide approved in a post-chemotherapy space. And very recently, at least in the US, within in the last couple of weeks it was approved in the pre-chemotherapy space as well. Add to that Radium 223. I forgot about the other one.
M: …with the bone seeking isotope.
R: Yes.
M: None of these agents are tested in a non-metastatic situation, yet?
R: Tested, yes. Validated, proven and approved, no. It is still kind of early on.
M: How many years for that?
R: Oh, a long time probably. The reality is with prostate cancer is that man who undergo treatment with curative attend be it surgery or radiation who then develop progression after that treatment and then go on to have life threatening form of the disease, that natural history plays out on the order of somewhat between 6 and 15 years. Early stage studies although they are very important they require a large sample size and a long follow up. Fortunately we have some of these studies that are under way: adjuvant chemotherapy studies etc. But, they are just in the period of time where we are in follow up mode, data collection mode and we do not have the answers for.
M: But at ASCO this year we did get a nice phase III trial using first Docetaxel plus Androgen-Deprivation Therapy.
R: Right.
M: That will change a little bit in terms of the multi-prescription.
R: Right. Well keep in mind that is not really an early stage patient population.
M: Correct.
R: That is an untreated metastatic group of patients. The metastatic castration-resistant group is late stage disease if you will, where the expected survival is on the border of 4 years, with the untreated metastatic disease; those are patients who still have hormonal therapy available to them. They are not resistant to the hormonal therapy. So it is a slightly different patient population.
M: You are presenting the final results of this really important trial – it must be important because you came all the way from San Francisco to tell us.
R: Right. Well, I would have gone anywhere to present it. This is the final analysis of a phase III randomized trial. It is the COU-302 study. We call it 302 study and the importance of this study is:
No 1) the patients in this state of the disease – these are patients who are asymptomatic or minimal symptomatic, they have not received prior chemotherapy and the goals of therapy for these patients are to preserve asymptomatic state, prevent complications from the disease, delay progression of the disease and of course improve survival. In previous analysis we have shown a very robust data demonstrating a delay in radiographic progression. That is highly statistically significant. We showed a very strong trend in favor of survival for abiraterone compared to the prednisone control. But the final analysis that we presented here now, shows that with 96% of the deaths having occurred we see a statistically significant improvement in survival. And this is despite a series of interim analyses. It was not always apparent this was going to be present. It demonstrates a couple of things. One is the therapy improves survival definitively statistically significant. No problem there. But it also demonstrates the power of completing a trial. The study was un-blinded 2 years ago. But the study was not terminated. Actually 2.5 years ago. And completing the study to its final conclusion is really important, because we have new data now.
M: Sure, and you got cross-over data, too.
R: We had cross-over data. There were 9% of patients who formally crossed over per protocol. However, in reality 44% of the patients initially allocated to the placebo arm have received treatment with abiraterone. These make the data even more impressive that 44% crossed over to the actual study being tested. There was a huge amount of cross over if you will to other active therapies. These 5 other treatments that have been demonstrated to improve survival, many patients got more than one of those.
M: But you could do analysis according to the intention to treat…
R: Absolutely.
M: And also, you developed a new strategic vision – the strategy for the future.
R: Yes.
M: That you are now saying: Ok, you have a castration-resistant patients with prostate cancer who got hopefully not any problems from the disease or may have minimum problems and then you are saying the standard of care is now ...?
R: The standard care for many patients is abiraterone in this setting. And again, getting back to my previous point, the use of this therapy in this group of patients preserves quality of live, preserves the good performance status, prevents the complications, etc. I think this is really an important point and it is different for example from treating – not to diminish the importance – but patients who have very advanced disease who are symptomatic. We of course want to alleviate those symptoms, but we would like to delay them if we could in the patients who do not have them yet.
M: This became standard care in the United States or on the way?
R: In the current era yes, it is one of the standard treatments for patients who are chemotherapy naïve. It is widely utilized and of course is now the foundation for combination strategies, etc.
M: And will those be combinations or will they be sequential use of the other active agents?
R: That is the big question in the field. Nobody has demonstrated in prostate cancer really the benefit of a combination strategy. However, most of the combinations that have been tested have been a drug with a survival benefit and another drug that does not has a proven survival benefit. Now we need to combine some of these 5 or 6 agents and see how that works. We need to further clarify who are the patients who benefit from this approach versus not. We need biomarkers to help us do that in that field as progressing as well.
M: I am delighted that you bring the drug back to Europe where it started. Congratulations!
R: Thank you very much.
M: I wish you well with the combination studies, because that could make things even better.
R: Absolutely. Let`s hope so. Thank you very much.
M: Thank you, Charles.