Emery Salom, MD, associate professor and clerkship director at the department and division of Gynecologic Oncology at FIU, talks about how a new type of therapy could help ovarian cancer patients delay the recurrence of their tumors.
The first thing I want to start off with if you could talk to me a little bit about PARP inhibitors. What exactly are they? What do they do?
SALOM: OK. So PARP inhibitors are a new class of medications in which their antibody mediated to block a specific function in the repair mechanism cells, which affect preferentially cancer cells.
And so, before I was reading that typically, it’s usually given during the second or third dose after chemo. Why is that?
SALOM: Well, so initially that the studies were done after the third cycles of chemotherapy in which ovarian cancer had recurred. And it was started then to show that there was a benefit in specific patients that had a BRCA mutation, which is breast ovarian cancer syndrome mutation, and so found to be the most responsive then. And as time has gone on, more studies have done. And now it moved into the second line. And now we’ve had a number of studies in the first line, meaning that patients who are initially diagnosed with ovarian cancer are operated on and then are started on chemotherapy are then started on what’s called maintenance therapy. And so maintenance therapy is that you receive the PARP inhibitor upfront as soon as you finish the first treatment as opposed to the second or third.
And what was the research that was done to figure that out to start as the first line treatment instead of waiting until after the second or third dose?
SALOM: So currently, there are three studies that have been done called the Prima, Paola and Velia Studies. And they all look at three medications that look at women who, again, have been diagnosed with advanced stage ovarian cancer in which they underwent surgery for staging or what’s called cytoreductive surgery to remove all visible tumor. And then they receive what’s called Up Front, and first-line therapy with chemotherapy, including paclitaxel and carboplatin. And then they’re started with these PARP inhibitors since they’re finished chemotherapy. And a few of these studies were done in which they did receive the PARP inhibitor during their first line therapy. And then they were continuing on maintenance therapy for about two years, either 15 months to two years.
And so, you touched on, a little bit like, how often are they giving these inhibitors? Is there a time frame that they’re on it?
SALOM: So the advantage that many patients that unlike intravenous chemotherapy, which is the standard, these patients can be taking oral medications that we call maintenance therapy. So, the ease to the patient. Certainly better than intravenous administrations. And they take it for up to 15 months as part of the largest or longest time that they’ll be taking it. It’s either they take it for that period of time or until we identify the recurrence of the tumor.
OK. And so, they have the chemotherapy. And it is through the IV, the chemotherapy, correct?
SALOM: Yeah. So, most chemotherapies traditionally are intravenous.
And then so after the chemotherapy, they’re giving these oral medications, which are the PARP inhibitors…
SALOM: Yes.
To at least try to prevent the recurrence of the cancer growth. And so are there particular patients that this would be ideal for? Are there some patients that this wouldn’t work better for?
SALOM: So, there’s initially it was designed or shown to be very responsive to patients who had this breast ovarian cancer syndrome mutation or in the family called homologous recombination deficiency patients in which we do now special genetic testing of the tumor itself as opposed to blood testing to see that hereditary system and a change in that specific mutation. We can do this testing on the tumor itself. And so if they’re either BRCA one or two positive or they have in the tumor itself show changes genetically that qualify under homologous recombination deficiency, those are the patients that do the best. But the initial studies now show that we give it to everyone, whether they have the mutation or not because they still have a good response at what’s called progression-free survival is increased in all three categories. But certainly, the people or the patients that have BRCA one or two or homologous recombination deficiency do the best.
And would there be any set of patients that wouldn’t necessarily get this?
SALOM: Yeah. Certainly, there’s a subset of patients that are not good candidates. And those are the people that may have had side effects from chemotherapy in which their blood counts are low or they’ve had allergies to these PARP inhibitors. Or if they received a previous PARP inhibitor for another disease process, then those are not candidates for the inhibitors.
And kind of leading up to my next question, are there any potential side effects?
SALOM: There certainly are. As we know, there’s many medications that cause side effects. Luckily, they’re very manageable, these side effects. But many of them include, since they’re an oral medication, they include some nausea and GI issues, occasionally diarrhea. And then we also do many blood test evaluations because it can cause anemia. They can lower your white cell count, and they can also lower platelets. And so we check these routinely as a patient’s receiving medication.
And would you have a percentage of patients that would get these as opposed to those who wouldn’t get these? What percentage of patients would typically get PARP inhibitors?
SALOM: Well, currently now it’s 100%. So, it’s generally recommended and can be used for everyone. And so the potential is that every patient can receive it. But if you look at the patients who will have the best response, that is those patients, the homologous recombination deficiency, or they have this BRCA one or two mutation. Those would cover about 20% percent of all ovarian cancers. And so that’s a subset of women that will do the best. But now it’s certainly recommended for all patients.
And is it only for ovarian cancer?
SALOM: It’s being now used for other tumors. And it’s being certainly used in breast cancers. And it’s being explored in several cancers and other GI cancers. So as the time goes on, I think we’ll see that its utility in other cancers certainly will expand.
And would it be just for those particular cancers or what about for prostate cancer or any other type of cancer?
SALOM: So prostate cancer also is receiving an indication because a lot of the prostate cancers also have this BRCA mutation or homologous recombination deficiency mutation. So there are many tumors now that are being explored and receiving an indication to use PARP inhibitors.
And what implications do we believe this would have as a first-line treatment for the oncology field?
SALOM: Yeah, so if you mean first-line therapy meaning that instead of using the traditional intravenous chemotherapy and just using these inhibitors, we’re certainly not there yet with regards to using that alone. But certainly, being used in combination with intravenous at the same time is also being explored currently, not FDA approved in general, but certainly being used upfront even after the first treatment or during the first treatment.
And fear of a recurrence for any cancer patient is just something that’s really terrible. And so what do you think this would do for a cancer patient’s peace of mind when they know that this can potentially help prevent them from getting recurrence of the cancer?
SALOM: Yeah. So that’s something that we didn’t have before. It’s standard therapy. A few years ago, was that you gave a patient intravenous chemotherapy, usually typically six cycles, and then you sit and wait. And unfortunately, in ovarian cancer at least, we know that they do very well upfront, meaning that we’ll give them intravenous chemotherapy even for these women who have very advanced disease called stage three, which is the most common stage we diagnose them, meaning they have obvious large tumor that’s in the abdomen, and we finish therapy. We give them chemotherapy, and more than 80% respond, but we have no more tumor. And in these set of women, we just observe, and we see them every three to four months. And a large proportion of these women will have a recurrence. And so it’s hard to sit there and know that there is a risk of it coming back and there’s nothing we’re doing about it. And now we have this opportunity to give something orally that we know will delay that recurrence for a long time, and I think that gives peace of mind to a lot of women knowing that they’re able to do something in the interim.
And is there any research as to seeing, like, you know, five years out, how is the survivor rate or the recurrence rate with these PARP inhibitors?
SALOM: Well, certainly, we have data at about two, three years. We don’t have mature data on these randomized studies as of yet. So we don’t have survival data yet. But that certainly will be reevaluated as time goes on.
And do you have any data on the recurrence rate from what you have so far, the two or three years out?
SALOM: Certainly. So the recurrence rate has been delayed. So the term we use is progression-free survival, and that or, ecurrence of the tumor, time to recurrence, if you will. So it’s not really survival but time to recurrence. And this has been reported that if you look at these patients on PARP inhibitors, on average, it’ll increase about six months to up to a more than a year depending on, again, if you are BRCA one positive patient or two. If you’re a homologous recombination or you just a patient that has neither, again, you go from three months to more than a year.
Anything I didn’t ask you that you feel that people should know?
SALOM: Yeah, I think the important thing for patients to focus on is that the, you know, the field luckily is always changing, and there’s always new therapy that is constantly being investigated and explored. And that, you know, I think with every year that pass we add more and more responses to chemotherapy and to the cancer. And that there’s always hope, and there’s always more treatment. So, maintenance therapy has been around in different cancers for sure. With ovarian cancer, we have something called Avastin, which has been used as maintenance therapy. And certainly, that has been present. We know that there is some benefit, especially in specific group of patients, especially when they’re stage four disease and a bit maybe less with stage three disease. So, the concept of maintenance therapy in cancer has been around. I think the difference here with these PARP inhibitors is that the patient doesn’t have to receive this intravenous therapy, like with Avastin. They have an oral substitute that they can take at home, and that the response rate in a subset of women is significant to delay the time to recurrence for more than a year, that otherwise you don’t have the opportunity to do so is a big deal in the world of cancer. So I would say yes.
Does this affect women with small cell ovarian cancer? Because that’s really deadly…
SALOM: So small cell ovarian cancer is a very rare tumor, exceedingly rare, so probably 1% to 2% of all ovarian cancers. And I don’t know if we have any particular studies with PARPs in small cell, so hard to tell.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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