Hi, I'm Dr. Scholz. I want to give you an update on a couple of new drugs that just
came out for advanced prostate cancer.
This is pretty exciting stuff. There aren't that many active agents for men with advanced
hormone-refractory prostate cancer. Xofigo, chemotherapy (taxotere and jevtana type stuff),
of course the old standards of Lupron, and then the very exciting second-generation hormonal
agents like Xtandi, Zytiga, Erleada, and Nubeqa. We also have Provenge which is an immune medicine.
But men with advanced hormone-refractory prostate cancer really need help. A lot of these things
run out of effectiveness and if you've gone through three or four of these, you're starting
to run out of choices.
So, these new medicines are pills. One is called rucaparib and the other one is called
olaparib. Coincidentally they both got FDA approved exactly the same week and that was
just last week. So, we're at a—it's really a breakthrough. A breakthrough for men with
advanced disease to have brand new medicines that work by a brand new mode of action. So,
what that means is that if they've developed resistance to one type of therapy, they're
likely to get a benefit with this other type of therapy.
So, well what are they and what do they do? Olaparib and Rucaparib work by blocking an
enzyme called PARP. PARP is the enzyme that helps repair DNA. Men that have a genetic
abnormality in their DNA reconstructive enzymes that have these mutations called BRCA don't
repair their DNA as effectively. Well, the cancer cells inherent that same gene and if
you give these PARP inhibitors such as rucaparib and olaparib, it further makes it more difficult
for the DNA to repair in the cancer cells when they try and replicate, and so these
PARP inhibitors are selectively causing the cancer cells to have trouble replicating whereas
the normal cells in the body which aren't replicating as quickly can tolerate these
medicines better than the cancer cells are able to tolerate it.
These medicines are only going to be effective in men that have a certain type of genetic
mutation called BRCA, and these medicines work in those individuals. I think it's about
20-25% of men that have these types of mutations when they become hormone-refractory. So, not
everyone is going to benefit, at least with coverage. It's actually not proven that you
have to have this mutation to benefit. Some men will probably respond without these mutations,
but right now, I think, insurance is only going to cover men who have these specific
mutations.
So how do you find out if you have the mutations? Pretty much it's just a simple blood test.
Gaurdant360, FoundationOne, and other companies have different types of blood tests that will
tell you if you have the BRCA mutation. So, when do you use these medicines? Well, they're
probably only going to be covered by insurance in men that have had a second-generation hormone
already (Xtandi, Zytiga, Nubeqa, Erleada) and have stopped responding. So, we're talking
about hormone-refractory, but also to the second-generation agents. And I believe that's
the setting where you're going to get insurance coverage and these no doubt are going to be
expensive.
What kind of side effects do these things have? Think of a mild type of chemotherapy.
Not an injected type, but a pill. And these medications, which are taken twice a day,
are going to cause some fatigue, maybe some anemia, possible for other low blood counts
(low white count, low platelet counts). Generally, they've been pretty well tolerated. There
have been some rashes, occasionally some irritation of the liver. People have to be monitored,
but the quality of life will be good and it is definitely extending life, causing the
cancer cells to regress, making PSAs decline. So, brand new medicine for prostate cancer.
Totally new, independent mechanism of action and it is going to be on the market; it is
already on the market, and this will be covered by insurance companies, so this is very good
news for prostate cancer patients who have advanced disease.