So Dr. Scholz, today we're talking about Xofigo—otherwise known as radium-223—and
we know that this drug has been out for many years now
and, really, can you explain the stage of men who would be receiving this and also how Xofigo works?
So, Xofigo is an injection of a radioactive substance—radium itself,
actually, pure radium—into the bloodstream once a month. It has a very specific property — it
tends to congregate or be attracted to areas of irritation in the bones
in a similar fashion that calcium would be attracted to those areas.
It's an alpha particle emitting type of radiation which is not—when we think of photon radiation,
the beam radiation, it's multiple little packets of energy—alpha particles are one big heavy
hitting emission of radiation. They say that a single alpha particle hit on a cell can be fatal.
Alpha particles are also interesting because they don't travel very far; they go a millimeter
or two and then they they dissipate which is a nice property so that you don't get a lot of
overspill of the radiation onto the bone marrow. So, the fact that it's attracted to areas of
irritation in the bone where the metastases are, and it has these other properties make
it very effective for treating prostate cancer through a single monthly injection.
What is the patient experience of taking Xofigo? You said it's an injection, how many times?
Yeah, the original studies they evaluated six monthly injections and
since that format was designed that's what's been followed ever since,
and it seems like a reasonable course of therapy. The experience of the patient
is one of a very brief intravenous injection. There's no immediate side effects, but over
the next couple of days a small percentage of patients will develop some low-grade nausea or
possibly a little bit of diarrhea; others don't really feel anything at all.
Is there anything that patients would need to take to supplement taking Xofigo? Can it weaken
the bones in any way or is it just going to hit those metastatic spots and they're good to go?
It's pretty much good to go. There was a study done mixing it with another
popular medicine called Zytiga and in that study they saw some increased
bone fractures. There are other factors; it's not clear if it was because of the Zytiga
or the fact that these patients were getting the treatment at a little earlier stage.
It was realized that many of the men in that study did not get bone protective agents like
Fosamax or Xgeva or Prolia, and those that did have much less of a problem, but it's typically
an inert substance apart from this one interaction that was seen in the Zytiga/Xofigo study.
So, can Xofigo treat any type of metastatic lesion? So lymph node versus bones?
So, it only works in the bones which fits pretty well with the profile of
many prostate cancer patients. The cancer that's in the lymph nodes is
less important, in other words it's not as dangerous as having bone metastases,
so you can tolerate some lymph node metastasis being left untreated because zofigo only treats
the bone. It's certainly not effective if someone had liver metastasis, a more serious
condition with prostate cancer patients; it's far less common. But generally, that's the
profile with most prostate cancer patients is the majority of their disease is in the bones.
So does Xofigo affect PSA?
So, Xofigo has a much smaller impact on PSA than other treatments except maybe Provenge
which also has a little impact on PSA. We'll occasionally see PSA responses with Xofigo,
but typically we don't, and that can create some confusion about is it actually working.
There's another bone marker called alkaline phosphatase that is commonly available in what
we call the hepatic panel—a routine liver test routine blood test for the liver—and
that may be a better signal if the alkaline phosphatase was previously elevated due to bone
involvement and it starts to improve or decline that the Xofigo is working in that scenario.
What would be the expected response rate of a patient who has some metastatic lesions,
take Xofigo, they're going to take the alkaline phosphate test,
what would the next steps be? What are we looking for?
Well, this is one of the the challenging things. First, Xofigo, if you look at prostate cancer as a
general spectrum of disease, when people have more advanced metastatic bone disease that's — you're
getting toward the end of the the line and far more serious type of cancer than we typically
think of, and so in the clinical trial that was done over in Europe to get FDA approval, a lot of
these people you know had PSAs of a 1000, they had very extensive bone disease and Xofigo was clearly
helpful in making people live longer; they didn't see a lot of impact in terms of PSA declines. It's
a medicine, therefore, that is a little tricky to figure out when it's really helping people.
We don't use it in people that have relatively limited bone metastasis because you can use
beam radiation to treat those spots, but if someone has extensive bone metastasis,
the absence of liver metastasis, not too excessive amounts of lymph node metastasis,
those people are good candidates for Xofigo, and this is the same type of
pattern you'll see in people that might be considering Taxotere or Jevtana chemotherapy.
Xofigo may be a little more attractive in that setting because it has,
you know, no hair loss, less tiredness than Taxotere and Jevtana, and it's a simple monthly
injection, so it's nice for quality of life and it has been documented to prolong life.
It's difficult in each individual patient, though, to know
is that one individual benefiting a little bit or a lot because of the ambiguity about PSA response.
With the current standard of care,
what is the sequence of drug treatments that would make somebody eligible to take Xofigo?
Well, you're eligible if you have metastatic disease and, you know,
the typical Lupron medications are no longer working. I would further prefer that a patient
have a significant number of bone metastases—not just two or three—but after that some patients may
have already had Xtandi or Zytiga, maybe some have already been treated with Taxotere and Jevtana,
and the doctors have flexibility in terms of deciding which sequence is going to be optimal
for patients. Zytiga and Xtandi are popular because they're just pills and typically they have
relatively few side effects. So, oftentimes you'll see patients be treated with Zytiga and Xtandi,
and at the juncture in time where the those medicines seem to be no longer working — natural
time to be thinking about something like Xofigo or possibly Taxotere at that stage.
So, are there any negative drug interactions, you know,
what does the quality of life look like when it comes to taking this treatment?
So, it's simple radium so there really aren't any drug interactions and it's, you know,
simple to administer. I think sometimes it gets overlooked; it is typically reserved for the more
advanced stages of prostate cancer and people are hustling around and trying to find answers,
sometimes this is a good treatment and it gets overlooked in that process which is unfortunate,
but it's well tolerated and convenient and it's probably underutilized.
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