Immunotherapy — Now, when I said that sometimes chemo carries a negative cloud on side-effects
and that turns out not to be true and I love the way you put it, "aspirin is chemo." I
think androgen deprivation therapy can also be perceived as chemo with all the side — I mean,
you use experience side effects. I think it's more tagged with side effects. We all have chemo,
but chemo comes with benefits, right? But immune therapy has the opposite problem,
everyone feels warm and fuzzy about it, and so, but I'm excited about it. Can you tell
us where we are with immune therapy? Because it looks like it has a role in Neurology; it looks
like as a role in bladder cancer, and is it gonna have a role in prostate? I think it will, right?
Yeah I think so. I mean it already has one agent FDA approved, Sipuleucel-T or Provenge.
Provenge, right.
Now that is an immunotherapy that, you know, is more like a vaccine therapy.
It's an educative process; you're trying to educate your own immune cells, your T
cells and B cells, to go after and recognize the protein expressed on the prostate cancer cells,
prostatic acid phosphatase. Okay, but I think when people are talking to you know therapy now
they're talking more the checkpoint inhibitors, you know, CTLA-4, PD-1, PD-L1, those sorts of
therapies where you have agents like pembrolizumab or Keytruda that have over 20 FDA approvals across
different cancers and the natural question is why not prostate? There's a lot of Investigation
in prostate. The early data shows that if you just treat a general population by itself with
those agents like Keytruda or pembrolizumab you don't get dramatic response rates. It's
probably more in the five to ten percent range, so you might need to do combination therapies;
you might need to do more selective therapies. Certain patients have mutations and mismatch
repair genes and these can lead to widespread hypermutation across the genome that provides
more targets for your immune system to go after and these drugs might work better in that patient
population. It could be as low as 3% of patients with metastatic prostate cancer; it could be
as high as ten or twelve percent of patients depending upon which studies you look at, but
I think those patients are ideal. There's another gene called CDK12 where some data that shows that
it's present in about 7% of men with metastatic castrate-resistant prostate cancer that leads
to a lot of kind of focal tandem duplications of the genome that are highly immunogenic, and that,
there's early investigation going on, but that might lead to good responses to immunotherapy
as well. So there's a few approaches, one of which is the combination drug approach to try to
make it work for a broad population. The other is the more targeted — find a genetic subset
of patients that are gonna respond well, and I think all this is ongoing, but it's promising.
But some people do qualify right now for Keytruda. I mean everyone's supposed to—if
they qualify for Provenge—they get it, that's great, it's been out, but you do
have a subset of patients that do qualify for some of these a new immune therapies, right?
Yeah, those with microsatellite instability; it's from these mismatch repair genes.
But how do I find out that I have microsatellite instability? How do I know I qualify?
Yes, similar testing as you find out if you have DNA repair deficiency. There's next-generation
sequencing technologies that will test your tumor, and most of these are targeted panels
maybe 300 cancer-associated genes that look at the look at DNA repair deficiency genes;
they look at mismatch repair genes — a whole host of other things that are involved as well,
and you know, there's technologies we have a homegrown one here that Colin Pritchard developed,
UW OncoPlex, but there's other ones out there — Memorial Sloan-Kettering has there's;
there's foundation medicine which is probably the broadest, easiest to access one. So,
usually these reports will not only give you information on the DNA repair genes,
but they'll give you information on microsatellite instability mismatch repair.