Hello, my name is Dr. Oliver Sartor. I am the Laborde professor for cancer research at the Tulane Cancer Center also medical director of the Tulane Cancer Center and I am in both the Departments of Urology and Medicine. I am reporting live from ASCO being held here in Chicago. I am going to be covering a couple analyses today. First of all I am going to be talking about the pain analysis from the phase III randomized ALSYMPCA study with Radium-223, and then I am going to be shifting over to the analysis of prior docetaxel on product parameters at the PROCEED registry, and then I am also going to be talking about phase II in nonmetastatic prostate cancer for individuals receiving orteronel.
So let us take these one by one, we will start out with the radium study and it is embedded within the context of the phase III ALSYMPCA study, let me explain what that is. The phase III ALSYMPCA study looked at radium or placebo in over 920 patients who were randomized to receive 6 doses of radium or 6 doses of placebo plus best supportive care. The overall survival has been reported, it is positive. The skeletal-related events have been reported and it is positive, and now we are going to be talking about pain. How is pain looked at? Pain was looked at in terms of a subscale within some of the quality of life parameters, four questions that assessed pain and this has been done before. The bottom line is, in addition to prolonging overall survival, in addition to diminishing the rate of skeletal-related events, that the radium, which also had a good safety profile, also diminished pain as measured by these parameters. It turns out that it was not just pain that was diminished, it was also the use of opioids. There is a very nice hazard ratio that will be presented in the poster, a very nice Kaplan-Meier curve and what you can say is it also has an opioid-sparing effect. So radium helps pain, decreases opioid use, prolongs survival with a good safety profile, and of course it is now FDA approved as of May 15th.
Next we will be going on to the analysis of docetaxel on some of the sipuleucel-T product parameters and this is really a very simple study. You are looking at the product parameters because you can upregulate certain antigens in the process of manufacturing sipuleucel-T. This is an in vitro analysis of how the product parameters look and it was simply looking at patients who had not received prior docetaxel or those who had received prior docetaxel; and a very simple conclusion, there really was no difference in the product parameters in those pretreated with docetaxel or not. Whether or not the clinical outcomes would not necessarily be the same, I cannot state, I can only talk about the product parameters, and they are the same.
Next, I would like to go on to a phase II analysis of orteronel, looking at both efficacy and quality of life in individuals with nonmetastatic castrate-resistant prostate cancer. The key thing we are going to look at here is the utilization of no steroids in this setting. Now we all know that CYP17 inhibitors and the use of steroids have been greatly discussed, particularly with abiraterone. There are two components to CYP17, there is the 17 alpha hydroxylase and the 17,20 lyase. If you are able to hit the lyase specifically you would probably would not need to be using steroids. The abiraterone has both the 17 alpha hydroxylase as well as the 17,20 ketolysis, pretty equally inhibits both enzymes. Really need to give it with a corticosteroid such as prednisone. On the other hand, orteronel is more favoring, hitting the 17,20 ketolysis and in this study they looked at it without steroids to see if it would be feasible. What did they find? The nice news is it worked. They were able to go without corticosteroids, people had very reasonable quality of life and most importantly, the patients were responding to therapy unequivocally by a variety of parameters we used, PSA, etc. Bottom line is, you are able to give orteronel without steroids at least in this setting, you do not have to use the steroids in order to get responses, and I think that is a nice take-home message.
So these three abstracts were ones that were selectively covered today, of course there are many, many more of interest. I wish you could be at ASCO, I have enjoyed being here. Thank you very much.
Efficacy and safety of radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases who did or did not receive prior docetaxel (D) in the phase III ALSYMPCA trial. http://meetinglibrary.asco.org/content/114175-132
Impact of prior docetaxel (D) on sipuleucel-T (sip-T) product parameters in PROCEED patients (pts). http://meetinglibrary.asco.org/content/108044-132