DR SARTOR: A lot of people may not be familiar with radium-223. Very interesting alpha particle, which is something we’ve never used in medicine before in any widespread sense, but a few small trials.
But this alpha particle is bone targeted. It binds to the inorganic matrix. It doesn’t bind to the tumor cell, per se. It goes into the osteoblastic lesion, particularly the area around the hydroxyapatite, which is calcium rich. Turns out that radium is really a calcium mimetic, very much like strontium in that sense.
But there was a large trial called the ALSYMPCA trial, Phase III, 921 patients. And very surprisingly, last June in an interim analysis — and I say surprising because I was hoping the trial would be positive, but at interim I really didn’t think it was going to be — last June, in 2011, the interim analysis was announced as positive by the IDMC. And the IDMC actually terminated the trial and recommended that the placebo patients crossed over to receive the radium.
What was presented at ASCO was really the updated analysis on the survival. Initially there were about 314, and this was a preplanned interim analysis, 314 events.
And then at ASCO there were 528 events for survival. And it moved the needle a little bit on the medians. Didn’t change the hazard ratios. The hazard ratio was 0.695 either way. Medians were 14.9 for the patients on the radium, 11.3 for the placebo.
Should mention just a tad about trial design, because it turned out there were some unusual elements about the trial design.
The patients had to have metastatic castrate-resistant prostate cancer, bony metastasis, no visceral mets. But on top of that they had to either have received docetaxel, be unfit for docetaxel or refused docetaxel. And so there were some elements in here that kind of moved beyond the usual regulatory must-be postdocetaxel.
The bottom line is: You have a prolongation in survival and a pretty remarkable, in my opinion anyway, adverse event profile.
There was a tiny bit of myelosuppression, literally about 2% Grade III/IV neutropenia, 6% Grade III/IV thrombocytopenia. Other than that there really wasn’t very much at all. A little tiny bit of diarrhea, Grade I/II mostly.
But anyway, bottom line is: This is a new agent, a novel mechanism of action, bone targeted in the sense that it’s very specific for bone metastatic castrate-resistant prostate cancer, and the regulatory process is ongoing. I’m anticipating it will be FDA approved next year.
DR LOVE: So question from oncologists: Any MDS cases?
DR SARTOR: No. Zero.
DR LOVE: And the issue about the relative lack of myelosuppression, can you talk a little bit more about why it doesn’t occur and the alpha particles and all?
DR SARTOR: Sure. So it turns out that what most people think about when they think about radioisotopes are beta particles and beta emitters — and the beta emitters will have paths that come into the hematopoetic region of the bone.
And it turns out that we’re talking about millimeters of penetration, maybe 0.5 millimeters, 2 millimeters. It turns out for the alpha particle we’re really talking about microns. And it’s a very, very short radius.
So you have a deposition of the alpha particle within that osteoblastic lesion. It is going to be present and then only go, honestly, about 4 or 5 cell diameters and deposit the entire energy within that very short range. It just doesn’t hit the hematopoetic portion in the marrow very much.