Role for PARP Inhibitors as Maintenance Therapy



Maurie Markman, MD: How do PARP inhibitors impact the landscape of ovarian cancer treatment, from your perspective, as of today?

Justin Chura, MD: When we’re talking about the recurrent setting and we’re talking about treatment, I sometimes view it as a chess match. I have to be thinking about what I am planning now. But also, I have to be thinking about what I am doing 3 and 4 moves down the road, if treatment works or it doesn’t work. What are my next moves, and how do I get there? And when I think about the disease, in that way of that chess match, certainly PARP inhibitors have given me many more options of how I can deploy them for the patient, whether it is treatment because the patient has either an inherited or a somatic BRCA mutation or the patient’s had a great response to their platinum-based therapy for their recurrence and I want to try to maintain their remission, and maintain their response, and then use the PARP inhibitor in that context.

We also have to remember that when we employ these maintenance strategies or treatment strategies, there are side effects. Even though it’s a pill, it still has chemotherapeutic side effects. Those can be profound. In patients, I’ve seen profound anemia from the PARP inhibitor, or a profound decrease in their platelet count. So, even though we sometimes underestimate the potential for side effects because it’s a pill, because they generally are well tolerated, we still have to be vigilant for side effects.

Maurie Markman, MD: This term maintenance versus treatment is relatively new in ovarian cancer, and certainly in gynecologic malignancy as well. Do you have a simple explanation for patients and their families? What’s the difference between treatment and maintenance in the setting we’re talking about now?

Justin Chura, MD: Maintenance, simplistically, is following a therapy, whether it’s a continuation of one or a combination with one of the drugs that the patient’s been on. The goal of maintenance is simply to maintain the response, maintain the remission that’s been achieved, and to keep the disease in-check, if you will. We know that if we can do that, we can hopefully prolong what we call progression-free survival, or at least prolong the interval from when a patient would have to switch to a different regimen. So, with maintenance, we’re building upon a response we’ve achieved and we’re trying to maintain where we are. I don’t know if that makes sense, or if that makes sense to you, Anya?

Anya Khomenko: Yes, it does.

Justin Chura, MD: Treatment is defined when we have a recurrence of the cancer based upon a CT scan and a patient’s symptoms, and we want to treat now to see if we can make symptoms better, and to see if we can make the disease smaller. We look at scans for that purpose.

Maurie Markman, MD: How does the availability of PARP inhibitors influence your conversation about maintenance therapy with patients?

Justin Chura, MD: Well, one of the key benefits is that the patients don’t have to return to the cancer center for an infusion every 3 weeks, or every month. They take the medication on their own. We still do follow up bloodwork and follow up monitoring, but it’s a much more convenient cycle of treatment. It’s tablets that the patient can take at home, and on her own. Having that as an option, as opposed to having to come back for infusions, and sort of the process around that, really changes how we think about maintenance from a tolerability standpoint and a feasibility standpoint.

When we talk about maintenance, the goal is to maintain this remission to extend the progression-free survival and hopefully the overall survival. But we want to do it in such a way that the patient still has a good quality of life. If the patient travels, or wants to do those types of things, but has to return to the center frequently for infusions, that makes maintenance much more laborious and much more toxic for their quality of life. Having a PARP inhibitor, which is an oral medication, is a great way to now employ maintenance therapy with a little less disruption on a person’s lifestyle and quality of life.

Maurie Markman, MD: On a scientific level, and certainly from an FDA approval level, the definition of “maintenance” comes from this idea of platinum sensitivity. For the patients and their families who are listening, what does platinum sensitive mean? Then, maintenance with a PARP inhibitor may make sense.

Justin Chura, MD: Platinum sensitive. There’s a couple of ways it can be defined. In a simple way, it means that the patient responds, or their cancer is sensitive to platinum-based therapy. When we treat somebody for recurrence of their cancer with a platinum-based regimen, it means that they have a response. We see things get smaller, less in size, or even completely diminished so that we don’t even see them on a scan.

Sensitive means that they respond to the platinum-based regimen. That’s where we can then use a PARP inhibitor for maintenance. Patients who are platinum-resistant, which means that their cancer has come back within 6 months of their primary therapy, or their cancer no longer responds to a platinum-based regimen, are not considered eligible for PARP inhibitors.

Maurie Markman, MD: What should patients ask their doctors? Suppose it’s not brought up because it’s sort of new. Do you have advice for patients on how they might bring this conversation up with health care professionals? They’ve heard about it. They listened to this program, or they watched this program. What might they say, to their doctors, about this concept of maintenance therapy?

Justin Chura, MD: The first and simplest question is, “Am I a candidate for a PARP inhibitor? Am I a candidate for this therapy?” And that’s just being inquisitive or being curious about what therapies are out there. I think that’s an important question to ask about any treatment that may be available for a patient. But I think asking that question, “Am I a candidate,” and, “Why or why not,” is important. It’s also important to make sure that the patient understands, “OK, if I’m not a candidate, this is why.” Or, “OK, I am a candidate.”

The next discussion is, “Let’s weigh some pros and cons of this.” What are the side effects of the different PARP inhibitors that are approved? And how severe do those side effects tend to be? And then, what are the potential benefits, in terms of months gained? Then, where do we weigh that in the balance? That’s where a patient’s own values, a patient’s own goals of treatment, really come into play.

Maurie Markman, MD: Anya, you’ve already talked about the fact that you have a BRCA mutation. You have not needed treatment with a PARP inhibitor, which is great. But it’s out there. You’ve obviously done your homework. What are your thoughts about this class of drugs, new drugs, etc?

Anya Khomenko: I think the latest advance with PARP Inhibitors is very exciting. And, of course, I and my whole family are encouraged and excited that we have, still, another weapon in the arsenal of this fight. So, yes, I understand that I might have a recurrence. The next step would be to look into one of the PARP inhibitors.

It’s just great that every year brings new advances in technology, and I’m hopeful that the next year will bring some more effective tools.

Transcript Edited for Clarity

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