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Ovarian Cancer: Recurrence After PARP Inhibition

Panelists: Bradley J. Monk, MD, FACOG, FACS, University of Arizona; Creighton University School of Medicine; Arizona Oncology; Kathleen N. Moore, MD, University of Oklahoma; Elena S. Ratner, MD, Yale University School of Medicine; Brian M. Slomovitz, MD, Sylvester Comprehensive Cancer Center, University of Miami Health System
Published: Friday, Jun 14, 2019



Transcript: 

Bradley J. Monk, MD, FACOG, FACS: So let’s transition to what happens after PARP [poly (ADP ribose) polymerase]. Most patients do recur, except in the SOLO-1 setting, after a PARP inhibitor. What’s your kind of go-to regimen after a PARP inhibitor?

Elena S. Ratner, MD: Just like you, I believe in platinum sensitivity as a biomarker. I usually go back to a platinum to see if they will, again, have a response.

Bradley J. Monk, MD, FACOG, FACS: You know, I was always taught that platinum is the most important agent, and now we’re teaching that the response is a very important biomarker. I’ve been impressed that medical oncologists are not quite as indoctrinated with the platinum over and over in treatment. I think that’s unfortunate.

Elena S. Ratner, MD: Absolutely.

Bradley J. Monk, MD, FACOG, FACS: How about PARP after PARP, Katie?

Kathleen N. Moore, MD: You mentioned the elephant in the room. PARP after PARP is the next elephant in the room, with SOLO-1 and patients doing very well. I hope many of them are cured, but some of them are going to recur. They may recur remote from their PARP, and they may respond to a platinum again. And so, would you re-treat them with a PARP for maintenance? I think I would. We don’t have data for that yet. The OReO trial with olaparib is ongoing, and that is looking at that exact question in both BRCA and BRCA wild type, interestingly. And so it will inform some of that question. There are other studies just launching that are looking at that question and looking at even specifically patients who progress on a PARP and then re-treatment. So would I use it? Yes. Would I like to have data about that? Yes, I would. I think it’s coming.

Bradley J. Monk, MD, FACOG, FACS: Brian, I think you’d agree that if you progress on a PARP inhibitor, it’s probably not going to work later, right?

Brian M. Slomovitz, MD: Well, I wouldn’t say that necessarily. I believe your group presented some data looking at PARP after PARP inhibition. I think there were some patients who were previously treated with a PARP. And I don’t mean to present your data...

Kathleen N. Moore, MD: That’s all right.

Brian M. Slomovitz, MD: You know better than I do, but in those patients who received a PARP, progressed, and then were re-treated with a PARP, there were some responders.

Bradley J. Monk, MD, FACOG, FACS: But they were rare.

Kathleen N. Moore, MD: So in our data, it was patients who had been exposed to a PARP inhibitor in frontline therapy. They’ve got their set number of cycles, they progressed remotely from the PARP, got re-treated with a PARP, and responded.

Bradley J. Monk, MD, FACOG, FACS: Yeah, I get asked all the time: “If I progress on olaparib, since maybe niraparib is a stronger PARP, could I switch?” It’s probably not going to work.

Elena S. Ratner, MD: I think it depends how long they responded to the original PARP. Were they on the full dose? Anecdotally, we only see women who, again, respond to a PARP once you’ve confirmed that they’re platinum sensitive again.

Bradley J. Monk, MD, FACOG, FACS: Right.

Kathleen N. Moore, MD: Once we work out modes of platinum resistance, you may progress on a PARP and then you respond beautifully to platinum again. And you need PARP plus a PI3-kinase inhibitor, or you need PARP plus an antiangiogenic inhibitor. And so we’re doing those studies. So I think we’re going to see PARP after PARP. It may not be monotherapy.

Elena S. Ratner, MD: Yeah, I agree.

Brian M. Slomovitz, MD: It needs to be investigated. I’m not going to do it in my practice now. It needs to be investigated, but I wouldn’t throw it away. There may be a subset of patients [who] will respond.

Bradley J. Monk, MD, FACOG, FACS: Thank you for that summa

Transcript Edited for Clarity

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Transcript: 

Bradley J. Monk, MD, FACOG, FACS: So let’s transition to what happens after PARP [poly (ADP ribose) polymerase]. Most patients do recur, except in the SOLO-1 setting, after a PARP inhibitor. What’s your kind of go-to regimen after a PARP inhibitor?

Elena S. Ratner, MD: Just like you, I believe in platinum sensitivity as a biomarker. I usually go back to a platinum to see if they will, again, have a response.

Bradley J. Monk, MD, FACOG, FACS: You know, I was always taught that platinum is the most important agent, and now we’re teaching that the response is a very important biomarker. I’ve been impressed that medical oncologists are not quite as indoctrinated with the platinum over and over in treatment. I think that’s unfortunate.

Elena S. Ratner, MD: Absolutely.

Bradley J. Monk, MD, FACOG, FACS: How about PARP after PARP, Katie?

Kathleen N. Moore, MD: You mentioned the elephant in the room. PARP after PARP is the next elephant in the room, with SOLO-1 and patients doing very well. I hope many of them are cured, but some of them are going to recur. They may recur remote from their PARP, and they may respond to a platinum again. And so, would you re-treat them with a PARP for maintenance? I think I would. We don’t have data for that yet. The OReO trial with olaparib is ongoing, and that is looking at that exact question in both BRCA and BRCA wild type, interestingly. And so it will inform some of that question. There are other studies just launching that are looking at that question and looking at even specifically patients who progress on a PARP and then re-treatment. So would I use it? Yes. Would I like to have data about that? Yes, I would. I think it’s coming.

Bradley J. Monk, MD, FACOG, FACS: Brian, I think you’d agree that if you progress on a PARP inhibitor, it’s probably not going to work later, right?

Brian M. Slomovitz, MD: Well, I wouldn’t say that necessarily. I believe your group presented some data looking at PARP after PARP inhibition. I think there were some patients who were previously treated with a PARP. And I don’t mean to present your data...

Kathleen N. Moore, MD: That’s all right.

Brian M. Slomovitz, MD: You know better than I do, but in those patients who received a PARP, progressed, and then were re-treated with a PARP, there were some responders.

Bradley J. Monk, MD, FACOG, FACS: But they were rare.

Kathleen N. Moore, MD: So in our data, it was patients who had been exposed to a PARP inhibitor in frontline therapy. They’ve got their set number of cycles, they progressed remotely from the PARP, got re-treated with a PARP, and responded.

Bradley J. Monk, MD, FACOG, FACS: Yeah, I get asked all the time: “If I progress on olaparib, since maybe niraparib is a stronger PARP, could I switch?” It’s probably not going to work.

Elena S. Ratner, MD: I think it depends how long they responded to the original PARP. Were they on the full dose? Anecdotally, we only see women who, again, respond to a PARP once you’ve confirmed that they’re platinum sensitive again.

Bradley J. Monk, MD, FACOG, FACS: Right.

Kathleen N. Moore, MD: Once we work out modes of platinum resistance, you may progress on a PARP and then you respond beautifully to platinum again. And you need PARP plus a PI3-kinase inhibitor, or you need PARP plus an antiangiogenic inhibitor. And so we’re doing those studies. So I think we’re going to see PARP after PARP. It may not be monotherapy.

Elena S. Ratner, MD: Yeah, I agree.

Brian M. Slomovitz, MD: It needs to be investigated. I’m not going to do it in my practice now. It needs to be investigated, but I wouldn’t throw it away. There may be a subset of patients [who] will respond.

Bradley J. Monk, MD, FACOG, FACS: Thank you for that summa

Transcript Edited for Clarity
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