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Recurrent Ovarian Cancer: PARP Inhibitor Maintenance Therapy

Insights From: Michael Birrer, MD, ONeal Comprehensive Cancer Center; Ursula A. Matulonis, MD, Dana-Farber Cancer Institute; Kathleen Moore, MD, Stephenson Cancer Center
Published: Friday, May 31, 2019



Transcript:

Kathleen Moore, MD: We currently have 3 PARP [poly (ADP-ribose) polymerase] inhibitors with FDA approval for use as what we call switch maintenance in patients who are felt to be appropriate for retreatment with platinum. So in patients who have received platinum reinduction therapy and have either a complete response to that therapy or a very good partial response, after a certain number of cycles it is left up to the discretion of the treating physician if they can be switched to a maintenance therapy with a PARP inhibitor. And all 3—olaparib, rucaparib, and niraparib—are approved in this setting.

And you really continue it until the patient progresses again or patient choice or toxicity. Because we know that unfortunately, once someone recurs, they’re going to recur again. And so with this therapy, patients always ask us, “How long am I going to be on this?” We’re going to continue it really as long as it’s providing clinical benefit, which is really until we see the disease starting to come back, at least that’s what we do currently.

The indication is interesting in that unlike the frontline indication, it’s really agnostic to biomarkers, so you don’t have to have a BRCA mutation, you don’t have to have evidence that your tumor has trouble fixing its DNA by virtue of 1 of those HRD [homologous recombination deficiency] assays. Really anybody with recurrent ovarian cancer who has responded to platinum is eligible for maintenance PARP inhibition. And that’s really because of the data.

In all 3 PARP inhibitors, in different ways, they studied patients with BRCA wild-type. So all 3 programs had patients with wild-type, and in all 3 programs you saw benefit, statistically and clinically relevant benefit, in the non-BRCA groups, even in the groups with patients who were non-BRCA and had no evidence of homologous recombination efficiency. So it was made available really to everyone and is an attractive choice. It’s an oral agent for our patients, as compared with observation. And it’s a little bit sobering if you look at how those 3 trials are very consistent. You shouldn’t compare trial to trial. But they’re very, very consistent in a sobering way in that the patients who received placebo had a median progression-free survival of only about 5.5 months in all 3 studies, and it didn’t differ if you had a BRCA mutation. So you would think, “Oh, that’s your best prognostic group. I bet they did fine with nothing.” They did not do fine. They also had a median progression-free survival that was less than 6 months.

When we use observation, or no therapy, we’re setting half of our patients up to be platinum-resistant potentially. And so I think shared decision making with patients is important. Some patients—I certainly have some—do not want maintenance; they want a break from us. And that’s fine if they understand the data. But really, it’s not the same level of recommendation in my opinion as offering PARP inhibitor maintenance. You can do this, or we can just keep an eye on you: Those aren’t equivalent options in my mind for a patient with ovarian cancer, and they need to understand the ramifications of that decision on their disease course.

Transcript Edited for Clarity.
 
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Transcript:

Kathleen Moore, MD: We currently have 3 PARP [poly (ADP-ribose) polymerase] inhibitors with FDA approval for use as what we call switch maintenance in patients who are felt to be appropriate for retreatment with platinum. So in patients who have received platinum reinduction therapy and have either a complete response to that therapy or a very good partial response, after a certain number of cycles it is left up to the discretion of the treating physician if they can be switched to a maintenance therapy with a PARP inhibitor. And all 3—olaparib, rucaparib, and niraparib—are approved in this setting.

And you really continue it until the patient progresses again or patient choice or toxicity. Because we know that unfortunately, once someone recurs, they’re going to recur again. And so with this therapy, patients always ask us, “How long am I going to be on this?” We’re going to continue it really as long as it’s providing clinical benefit, which is really until we see the disease starting to come back, at least that’s what we do currently.

The indication is interesting in that unlike the frontline indication, it’s really agnostic to biomarkers, so you don’t have to have a BRCA mutation, you don’t have to have evidence that your tumor has trouble fixing its DNA by virtue of 1 of those HRD [homologous recombination deficiency] assays. Really anybody with recurrent ovarian cancer who has responded to platinum is eligible for maintenance PARP inhibition. And that’s really because of the data.

In all 3 PARP inhibitors, in different ways, they studied patients with BRCA wild-type. So all 3 programs had patients with wild-type, and in all 3 programs you saw benefit, statistically and clinically relevant benefit, in the non-BRCA groups, even in the groups with patients who were non-BRCA and had no evidence of homologous recombination efficiency. So it was made available really to everyone and is an attractive choice. It’s an oral agent for our patients, as compared with observation. And it’s a little bit sobering if you look at how those 3 trials are very consistent. You shouldn’t compare trial to trial. But they’re very, very consistent in a sobering way in that the patients who received placebo had a median progression-free survival of only about 5.5 months in all 3 studies, and it didn’t differ if you had a BRCA mutation. So you would think, “Oh, that’s your best prognostic group. I bet they did fine with nothing.” They did not do fine. They also had a median progression-free survival that was less than 6 months.

When we use observation, or no therapy, we’re setting half of our patients up to be platinum-resistant potentially. And so I think shared decision making with patients is important. Some patients—I certainly have some—do not want maintenance; they want a break from us. And that’s fine if they understand the data. But really, it’s not the same level of recommendation in my opinion as offering PARP inhibitor maintenance. You can do this, or we can just keep an eye on you: Those aren’t equivalent options in my mind for a patient with ovarian cancer, and they need to understand the ramifications of that decision on their disease course.

Transcript Edited for Clarity.
 
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