If we know somebody has DNA damage alterations, I think we are going to start going the route of PARP inhibitor and/or platinum or platinum-like agents like carboplatin, which have also been shown to be effective in patients with ovarian cancer with DNA repair defects. We are assuming that they are going to be equally effective as PARP inhibitors in prostate cancers, but that still has not been shown yet.
What results have been seen with PARP inhibitors?
In one trial, 14 out of 16 patients responded to olaparib. The 16 patients all had DNA repair alterations. That is a very high response rate, it is a small study and we do not have survival data but anecdotally, many of us who frequently treat prostate cancer have used a PARP inhibitor and had some prolonged, very good responses in patients who looked like they had pretty bad disease.
What has been seen with isotope therapy?
The isotope that I discussed was radium-223, which is an alpha emitter that was shown in a phase III trial to extend survival. Other radioisotopes that we have available to us, samarium and strontium, tend to be used—if used at all—toward the end of life when we are trying to quickly palliate bone pain. Radium-223 is a very different kind of agent—trials have shown there is a survival advantage in those who got radium in addition to best supportive care.
So, we need to think of using radium-223 earlier in the disease, not at the end, considering it takes 5 months to take all 6 doses. And, we need to now look at some combination trails because radium only goes to bone, and if a patient has disease outside the bone it would be great to understand what a combination—such as radium-223 plus abiraterone—will do for those patients. There is a phase III trial that is ongoing looking at abiraterone versus the combination of abiraterone and radium-223. That trial is fully accrued and hopefully in the next few years we will see results.
How do you see the future of radioisotope therapy progressing?
One of the things I did caution was that we have studied radium-223 in combination with docetaxel, and we found that there can be some significant myelotoxicities that were perhaps, a little unexpected. This is because, in general, radium-223 is not very myelotoxic at all. It is not really recommended that people combine docetaxel with radium-223 right now, but we are going to learn how to better use the combination of radium-223 and chemotherapy with more trials. Right now, I wouldn’t suggest that oncologists use this outside of a clinical trial setting, it could be potentially dangerous.