103 ESMO Parker Transcript
Kristine Crane: Prostrate cancer news took center stage at the recent ECCO-ESMO Cancer Congress in Stockholm. An international Phase three trial called ALSYMPCA showed that radium-223, also known as Alpharadin, conferred a thirty percent improvement in overall survival in advanced prostate cancer patients with bone metastases, compared to patients on standard treatment. Radium-223, which is made by Bayer, is the first treatment for these patients that shows survival benefit. And the patients who took radium-223 also had fewer side effects than patients on standard treatment. According to Dr. Chris Parker, the principal investigator of the ALSYMPCA trial, radium-223 is likely to become standard treatment for men with prostate cancer and bone metastases. At the ECCO-ESMO meeting I spoke with Dr. Parker, who is also an oncologist at the Royal Marsden Cancer Center in London. Tell me about the trial, what did you find?
Chris Parker: The ALSYMPCA trial was done in men with castration refractory metastatic prostate cancer with bone metastases. And they're all receiving their best standard care via further hormonal manipulation radiotherapy, bisphosphonates, whatever. And in addition they are randomized two to one to receive either radium or placebo. And the treatment was given by injection once every four weeks for a total of six injections. So the trial included nine hundred patients in all; six hundred on radium-223, three hundred on placebo. The main finding was an improvement in overall survival, with a hazard ratio 0.695. And perhaps the most interesting secondary endpoint was an impact also in time first skeletal-related events, with a delay of more than five months of the median. So really very exciting evidence of efficacy. And on the safety side, an extremely benign safety profile. So there were more adverse events in the placebo group than in the intervention group. We saw some…
Kristine Crane: Can you explain that?
Chris Parker: So that can easily be explained by the fact that we've got an effective treatment that reduces disease-related adverse events, and a well-tolerated treatment with very few drug-related events. So the only drug-related events of note, there was an increase in mild diarrhea and vomiting, although nothing serious, and there was a very small increase in minor toxicity. And so grade 3 or 4 thrombocytopenia was seen in four percent of patients on radium, and two percent on placebo. It was a global trial. It was done in nineteen countries throughout the world, including the states.
Kristine Crane: So this was the first Phase three trial, and are there other ongoing trials with other types of cancer?
Chris Parker: This is the only Phase three trial. There are also two ongoing earlier studies. There's a Phase two study in breast cancer, and there's a Phase one study in combination with docetaxel in prostate cancer.
Kristine Crane: Can you talk about the survival benefits, what those numbers mean?
Chris Parker: So hazard ratio is 0.695, translates to a thirty percent improvement in overall survival. The median survival in the placebo group was 11.2 months, and 14 months in the radium group. I think this represents a meaningful advantage particularly for an agent with such a favorable toxicity profile, and I think it's also worth saying we don't know for sure what the optimum dose scheduling is, and also what the optimum combination therapy would be. So it's quite possible, looking forward a few years, that we might get bigger gains from radium-223.
Kristine Crane: Why was the trial stopped early?
Chris Parker: The ALSYMPCA trial was stopped early because of a positive interim analysis. And having been stopped, patients who were allocated a placebo and who are still alive, will be offered the chance to have radium-223.
Kristine Crane: Could you talk about the pathology of prostate cancer, why does it go to the bone?
Chris Parker: So I can't answer the question, because we don't know why prostate cancer goes to the bone. All I can say is that in more than ninety percent of men with advanced prostate cancer, it does go to the bone. And in many of them it appears that bone disease is the only sited disease as far as we can tell. So it was obviously the most attractive disease in which to study radium-223. Having said that, radium-223 ought to be effective in bone metastases from other cancers. But in other cancers it may have less impact on survival because of disease elsewhere.
Kristine Crane: Can you talk a little bit about what's next in terms of other trials perhaps, or just the regulatory situation?
Chris Parker: So radium-223 does need to go through the regulatory process. I'm very optimistic that it'll go through it successfully, but I guess realistically it's going to take six to nine months, possibly even slightly longer, before it's licensed. I've no doubt that there will be further trials of radium-223 given these exciting results, but right now I can't tell you what those trials are going to be.
Kristine Crane: How did the ALSYMPCA trial differ from other prostate cancer trials?
Chris Parker: One way in which ALSYMPCA trial differed from other prostate cancer trials is that it wasn't restricted to the post-docetaxel setting. So ALSYMPCA included patients who are post-docetaxel, but also patients who are what I call non-docetaxel; that is to say they've not received docetaxel, but nor were they ever going to. And I think that's an interesting group of patients. I think it's a very large group of patients. I think around about half of all men with advanced prostate cancer never get chemotherapy, never see an oncologist. And so I anticipate that radium-223, assuming it is approved, will be used widely not just in the post-docetaxel setting, but also in the non-docetaxel setting. And that might even be where it's used its greatest, at least initially.
Kristine Crane: That was Dr. Chris Parker, an oncologist at London's Royal Marsden Cancer Center, speaking from the ECCO-ESMO meeting in Stockholm. For a transcript of this interview or to listen to other JNCI podcasts, please visit our website at www.jnci.oxfordjournals.org. This is Kristine Crane. Thank you for listening.
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