DR PETRYLAK: This patient was a gentleman who had initially presented with a spinal cord compression and had a decompressive laminectomy and then went on hormone therapy and subsequently went on chemotherapy at progression. And then we had a decision as to whether he should go on isotope with samarium or radium-223 chloride or possibly be referred for an MDV-3100 study.
DR LOVE: At that point, was he symptomatic?
DR PETRYLAK: He was symptomatic with pain at that particular point. He had diffuse pain, and he was on narcotic analgesics for that.
So we actually had referred him for treatment with RAD-223. And my predominant logic with that was that he had had an epidural compression before. And I think one of the more unique aspects of the ALSYMPCA trial, on the subgroup analysis, is the fact that there was a reduced rate of spinal cord compression on that particular trial. And I think that this is one of the unique aspects of this drug. This has never been reported with any other Phase III trial, specifically for cord compressions.
DR LOVE: So what happened with this man?
DR PETRYLAK: He was treated. He had some improvement in pain control.
DR LOVE: And what are you thinking in terms of how you might utilize this agent if it’s approved?
DR PETRYLAK: That’s a great question. I certainly am going to use this in patients who may not tolerate chemotherapy, if they’ve had extensive treatment beforehand. But my real question is, should we be moving this up front earlier, before chemotherapy? And again, the questions that we have about sequencing and about bone marrow suppression over time really clearly need to be answered, because we’ve traditionally used isotopes late in these patients to relieve symptoms. And perhaps what we should be doing is making the bone environment unfriendly to cancer cells further implanting and growing. And I think that that’s probably the most fertile area for clinical trial development.
DR LOVE: Matt, what are you thinking in terms of how you might want to use this?
DR SMITH: This was a study in patients who were late. The median survival in both arms was around a year. So this was a very high-risk patient population. I envision using it in patients who progress on chemotherapy or who are taking a holiday from chemotherapy, if they had a good response. Remember, these are 6 monthly treatments as the planned treatment duration, so in order to achieve patient benefit you’re going to try to treat the patient for about 6 months. So you want to look at the patients who have that window of time to do so. I think it is a reasonable therapeutic option for patients who are poor candidates for chemotherapy. I do worry about that as a regulatory issue, and I look forward to seeing how the FDA reviews that.
From a clinical perspective, though, it is a real and practical problem. There’s a substantial subset of patients who are too old and frail to safely receive chemotherapy, and there are some patients who just choose not to receive chemotherapy. But I would envision it, preferentially, using it in patients who have progressed on chemotherapy or who are on a holiday from chemotherapy and certainly would use it primarily or exclusively in patients with bone-only or bone-dominant disease.