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Approaching Platinum-Sensitive Recurrent Ovarian Cancer

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: Tuesday, May 28, 2019



Transcript: 

Bradley J. Monk, MD, FACOG, FACS: My theme is to leave nobody behind. My theme is to try to maximize the opportunity for my patients to be 1 of these long-term responders with either bevacizumab or PARP [poly (ADP-ribose polymerase] or maybe both. But in today’s world, you said it’s unethical, almost, to not test and to not give olaparib in the frontline BRCA-positive group. Do you feel the same in platinum-sensitive, PARP-naïve patients? We now have 3 FDA approvals: NOVA, niraparib; ARIEL3, rucaparib; and SOLO2 and Study 19, olaparib. Is it as equally unethical to observe that patient after a response to second-line platinum?

Elena S. Ratner, MD: That’s a more complicated question. Yes, I think it’s equally unethical not to give women with BRCA germline, somatic, HRD [homologous recombination deficiency]–positive mutations. And I actually think all of those. We know so little about homologous recombination deficiency, that there are going to be subsets of women within that group who are going to respond beautifully. We all have seen them. I think the bigger debate is women who are truly BRCA wild type and homologous recombination proficient. That could be the debate of the 3 months. I believe it to be the benefit for all of my women because I feel like we know so little, and there [are] going to be women there who will benefit even if we don’t know that.

Bradley J. Monk, MD, FACOG, FACS: Leave no one behind.

Elena S. Ratner, MD: Leave no one behind.

Bradley J. Monk, MD, FACOG, FACS: And to your point, yes, this HRD signature might be able to predict, but we can’t do that. Even in the BRCA-negative, HRD-negative patients who respond to second-line platinum, which in and of itself is a biomarker….

Elena S. Ratner, MD: Exactly.

Bradley J. Monk, MD, FACOG, FACS: Patients can do well for a long time.

Elena S. Ratner, MD: Yes.

Brian M. Slomovitz, MD: Yes.

Bradley J. Monk, MD, FACOG, FACS: Is it ever acceptable to take a patient and observe them?

Kathleen N. Moore, MD: Is it acceptable? It is acceptable if the patient chooses that.

Bradley J. Monk, MD, FACOG, FACS: OK, fine.

Kathleen N. Moore, MD: The NCCN [National Comprehensive Cancer Network] Guidelines actually list it as an alternative. I don’t think it’s an equivalent alternative, personally. Again, there are all these primary analyses, and then what you really learn from the studies. So you just listed NOVA, ARIEL3, and SOLO2. SOLO2, most importantly, in a BRCA population—all the patients who we apparently cure do amazing with nothing. If you give them nothing or placebo, their median progression-free survival is 5.5 months.

Bradley J. Monk, MD, FACOG, FACS: All of them were 5.5 months.

Kathleen N. Moore, MD: Exactly the same as the other 2. They do no better.

Bradley J. Monk, MD, FACOG, FACS: They do no better.

Kathleen N. Moore, MD: And so you set patients up to be subsequently resistant to platinum by just leaving them on nothing. And so I think we’ve learned that now, and maintenance has a much more important role than “You could get therapy or not get therapy.” If you tell a patient that, they’re going to say, “Well, I don’t want any therapy.” But you have to tell them what the ramifications are. Some patients need a break, and it’s shared decision making. They want a break. So do I think that’s acceptable? Sure. It’s their choice. I would never present that as the equivalent option.

Bradley J. Monk, MD, FACOG, FACS: The preferred option.

Kathleen N. Moore, MD: No.

Bradley J. Monk, MD, FACOG, FACS: So we have 2 elephants in the room with second-line platinum-sensitive relapse. One is bevacizumab versus PARP, and the second is, which PARP? Brian, I’m going to have you take the bevacizumab versus PARP question. If you have a bevacizumab and PARP-naïve patient in good performance status, no contraindications, and she says, “Dr Slomovitz, you’re world-famous. You’re in charge of the service at [the Sylvester Comprehensive Cancer Center at the University of Miami]. Which 1 do you want me to go on? Do you want me to get bevacizumab à la OCEANS or GOG-213 [Gynecologic Oncology Group Study 213], of this carboplatin–PLD [pegylated liposomal doxorubicin]–bevacizumab? Or do you want me to respond? And then I’m going to get 1 of the 3 PARPS. How do you answer that? It’s the elephant in the room.

Brian M. Slomovitz, MD: When I look at all my patients with ovarian cancer, I don’t look at them specifically in a vacuum at that line of therapy. I feel strongly that all women with advanced ovarian cancer, in their treatment course, deserve, at some point, bevacizumab. And at some point they deserve a PARP inhibitor.

Bradley J. Monk, MD, FACOG, FACS: Leave no one behind.

Brian M. Slomovitz, MD: I believe that all women, regardless of their status, HRD, deserve bevacizumab and a PARP inhibitor. Right now, the way that the guidelines are written, the only time that we could give them a PARP inhibitor, all women, is after a platinum-sensitive response. Based on that—again, you want me to tell you what’s happening in that room. I’m looking across the course of their disease. My frame of thinking being that I’m giving them bevacizumab in the frontline, except if they’re a BRCA patient, because the SOLO-1 data are game-changing. We’re seeing treatments where we never treated this disease before. I’m giving them bevacizumab in the frontline, and I’m giving PARP in their second-line of therapy.

To answer the question more specifically, if for some reason a patient didn’t get bevacizumab in the frontline, I’m really not sure of the right answer regarding what to give them in the second-line maintenance setting, bevacizumab or PARP. I’d probably lean toward a PARP because that’s my opportunity right now, to give them the PARP.

Bradley J. Monk, MD, FACOG, FACS: What do you think of that?

Elena S. Ratner, MD: I do exactly the same. I save my bevacizumab for the women who become platinum resistant, for whom you know that’s actually going to make a difference, and I do that the same with...

Bradley J. Monk, MD, FACOG, FACS: Or frontline, in the high-risk patients.

Elena S. Ratner, MD: Or frontline, of course. Katie, you said it so beautifully—about the shared model and decision making. But I think a big part of the patients in this recurrent setting and appreciating is that the cancer is never gone. I think all the recent studies on circulating change my conversation with the patient. I say to her, “You know what? We see nothing on the CT [computed tomography] scan. But I know from studies that unfortunately there are still cells, and the cells will come back.” I think that kind of changes the conversation.

Bradley J. Monk, MD, FACOG, FACS: So I worked on all these labels, and people would always say, “Monk, is it maintenance or treatment?” And if you look at the label, it says “maintenance treatment.”

Transcript Edited for Clarity

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Transcript: 

Bradley J. Monk, MD, FACOG, FACS: My theme is to leave nobody behind. My theme is to try to maximize the opportunity for my patients to be 1 of these long-term responders with either bevacizumab or PARP [poly (ADP-ribose polymerase] or maybe both. But in today’s world, you said it’s unethical, almost, to not test and to not give olaparib in the frontline BRCA-positive group. Do you feel the same in platinum-sensitive, PARP-naïve patients? We now have 3 FDA approvals: NOVA, niraparib; ARIEL3, rucaparib; and SOLO2 and Study 19, olaparib. Is it as equally unethical to observe that patient after a response to second-line platinum?

Elena S. Ratner, MD: That’s a more complicated question. Yes, I think it’s equally unethical not to give women with BRCA germline, somatic, HRD [homologous recombination deficiency]–positive mutations. And I actually think all of those. We know so little about homologous recombination deficiency, that there are going to be subsets of women within that group who are going to respond beautifully. We all have seen them. I think the bigger debate is women who are truly BRCA wild type and homologous recombination proficient. That could be the debate of the 3 months. I believe it to be the benefit for all of my women because I feel like we know so little, and there [are] going to be women there who will benefit even if we don’t know that.

Bradley J. Monk, MD, FACOG, FACS: Leave no one behind.

Elena S. Ratner, MD: Leave no one behind.

Bradley J. Monk, MD, FACOG, FACS: And to your point, yes, this HRD signature might be able to predict, but we can’t do that. Even in the BRCA-negative, HRD-negative patients who respond to second-line platinum, which in and of itself is a biomarker….

Elena S. Ratner, MD: Exactly.

Bradley J. Monk, MD, FACOG, FACS: Patients can do well for a long time.

Elena S. Ratner, MD: Yes.

Brian M. Slomovitz, MD: Yes.

Bradley J. Monk, MD, FACOG, FACS: Is it ever acceptable to take a patient and observe them?

Kathleen N. Moore, MD: Is it acceptable? It is acceptable if the patient chooses that.

Bradley J. Monk, MD, FACOG, FACS: OK, fine.

Kathleen N. Moore, MD: The NCCN [National Comprehensive Cancer Network] Guidelines actually list it as an alternative. I don’t think it’s an equivalent alternative, personally. Again, there are all these primary analyses, and then what you really learn from the studies. So you just listed NOVA, ARIEL3, and SOLO2. SOLO2, most importantly, in a BRCA population—all the patients who we apparently cure do amazing with nothing. If you give them nothing or placebo, their median progression-free survival is 5.5 months.

Bradley J. Monk, MD, FACOG, FACS: All of them were 5.5 months.

Kathleen N. Moore, MD: Exactly the same as the other 2. They do no better.

Bradley J. Monk, MD, FACOG, FACS: They do no better.

Kathleen N. Moore, MD: And so you set patients up to be subsequently resistant to platinum by just leaving them on nothing. And so I think we’ve learned that now, and maintenance has a much more important role than “You could get therapy or not get therapy.” If you tell a patient that, they’re going to say, “Well, I don’t want any therapy.” But you have to tell them what the ramifications are. Some patients need a break, and it’s shared decision making. They want a break. So do I think that’s acceptable? Sure. It’s their choice. I would never present that as the equivalent option.

Bradley J. Monk, MD, FACOG, FACS: The preferred option.

Kathleen N. Moore, MD: No.

Bradley J. Monk, MD, FACOG, FACS: So we have 2 elephants in the room with second-line platinum-sensitive relapse. One is bevacizumab versus PARP, and the second is, which PARP? Brian, I’m going to have you take the bevacizumab versus PARP question. If you have a bevacizumab and PARP-naïve patient in good performance status, no contraindications, and she says, “Dr Slomovitz, you’re world-famous. You’re in charge of the service at [the Sylvester Comprehensive Cancer Center at the University of Miami]. Which 1 do you want me to go on? Do you want me to get bevacizumab à la OCEANS or GOG-213 [Gynecologic Oncology Group Study 213], of this carboplatin–PLD [pegylated liposomal doxorubicin]–bevacizumab? Or do you want me to respond? And then I’m going to get 1 of the 3 PARPS. How do you answer that? It’s the elephant in the room.

Brian M. Slomovitz, MD: When I look at all my patients with ovarian cancer, I don’t look at them specifically in a vacuum at that line of therapy. I feel strongly that all women with advanced ovarian cancer, in their treatment course, deserve, at some point, bevacizumab. And at some point they deserve a PARP inhibitor.

Bradley J. Monk, MD, FACOG, FACS: Leave no one behind.

Brian M. Slomovitz, MD: I believe that all women, regardless of their status, HRD, deserve bevacizumab and a PARP inhibitor. Right now, the way that the guidelines are written, the only time that we could give them a PARP inhibitor, all women, is after a platinum-sensitive response. Based on that—again, you want me to tell you what’s happening in that room. I’m looking across the course of their disease. My frame of thinking being that I’m giving them bevacizumab in the frontline, except if they’re a BRCA patient, because the SOLO-1 data are game-changing. We’re seeing treatments where we never treated this disease before. I’m giving them bevacizumab in the frontline, and I’m giving PARP in their second-line of therapy.

To answer the question more specifically, if for some reason a patient didn’t get bevacizumab in the frontline, I’m really not sure of the right answer regarding what to give them in the second-line maintenance setting, bevacizumab or PARP. I’d probably lean toward a PARP because that’s my opportunity right now, to give them the PARP.

Bradley J. Monk, MD, FACOG, FACS: What do you think of that?

Elena S. Ratner, MD: I do exactly the same. I save my bevacizumab for the women who become platinum resistant, for whom you know that’s actually going to make a difference, and I do that the same with...

Bradley J. Monk, MD, FACOG, FACS: Or frontline, in the high-risk patients.

Elena S. Ratner, MD: Or frontline, of course. Katie, you said it so beautifully—about the shared model and decision making. But I think a big part of the patients in this recurrent setting and appreciating is that the cancer is never gone. I think all the recent studies on circulating change my conversation with the patient. I say to her, “You know what? We see nothing on the CT [computed tomography] scan. But I know from studies that unfortunately there are still cells, and the cells will come back.” I think that kind of changes the conversation.

Bradley J. Monk, MD, FACOG, FACS: So I worked on all these labels, and people would always say, “Monk, is it maintenance or treatment?” And if you look at the label, it says “maintenance treatment.”

Transcript Edited for Clarity
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