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Ovarian Cancer: Selecting Between Available PARPs

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, Jun 04, 2019



Transcript: 

Bradley J. Monk, MD, FACOG, FACS: Katie, the second elephant in the room is: Which PARP [poly (ADP-ribose) polymerase]? It’s unprecedented that we have medications with virtually identical labels. We have olaparib, rucaparib, and niraparib for patients who respond to second-line platinum. Tell me the things you consider in choosing 1 PARP inhibitor over another. And I apologize for putting you on the spot, but that’s what these guys want to know.

Kathleen N. Moore, MD: What do you think about when you’re choosing a medication? You think about efficacy; you think about adverse effects. What we know, again, from a lot of data across all 3 PARP inhibitors is that these are all very good drugs. There’s not, of the 3 of them, a best PARP and a least-best PARP. They all work, as best as we can tell, equally well. When you look at the BRCA hazard ratios for maintenance and for rucaparib—and actually all 3 of them now; the QUADRA data will be out soon—and the BRCA response rates in treatment, the maintenance hazard ratios are almost identical. If you look at HRD [homologous recombination deficiency]–positive in the maintenance, they’re almost identical.

The efficacy of all 3 of them is very, very similar across treatment lines. I don’t really think you can pick based on that. Prior to the “weights and plates” [body weights and platelets] analysis, the RADAR analysis with niraparib—which was a response to the high prevalence of thrombocytopenia in NOVA—I think that was sort of a way to discriminate on an adverse-event standpoint among the 3 PARP inhibitors because the other 2 didn’t have that high-grade toxicity. You presented the PRIMA data, which is frontline with that modification in from the beginning, not a reaction to the platelets. From the beginning, we individualized dosing and have demonstrated that the hematologic toxicities look really—again, if you compare with SOLO-1, which is the other frontline—identical.

I don’t know that you can discriminate them based on key adverse events. There are some differences. Niraparib has some hypertension and thrombocytopenia. Rucaparib has the transaminase elevation. There’s some anemia with SOLO-1. But none of them really kind of make you pick 1 over the other. It honestly comes down to what you’re comfortable with. So if you are comfortable with olaparib, use olaparib. If you’re comfortable with niraparib, use niraparib because that’s what’s going to help your patients stay on longer—your familiarity and your ability to set expectations, manage adverse effects, and help her feel comfortable that she’s on the right medication. You’re kind of guessing between the 3 PARPs.

Bradley J. Monk, MD, FACOG, FACS: So lots of talking points. You said activity and toxicity, and then you said that the most common dose of niraparib was 200 [mg], and you can get there faster by starting at 200 [mg] if the patient weighs less than 77 kg. Or you have got to have both—a baseline platelet count of 150 [x 109 L].

Kathleen N. Moore, MD: Right.

Bradley J. Monk, MD, FACOG, FACS: And once you personalized proactively the dose, then the toxicities are more similar. And then you said activity. And then you added a third: familiarity. There are others.

Kathleen N. Moore, MD: That’s true.

Bradley J. Monk, MD, FACOG, FACS: Brian, what do you think about this idea that in the non-BRCA patients, which is most patients, niraparib is more lipophilic and has higher intratumoral concentrations, and that’s why it’s once daily. And that NOVA was the only trial really to isolate the treatment effect in the non-BRCA cohort. Does that resonate with you? Is there a story there? I’m not asking you whether niraparib is your choice, but is there a story there?

Brian M. Slomovitz, MD: As far as my choice, I use all 3, based on the indications that they’re approved for. As far as the niraparib data, maybe it is broader in all comers, and you may allow for the BRCA wild type. I will use it, perhaps, in there more in that setting. But I’m not sure of the right answer. I’m not sure if it’s the lipophilic absorption within the cell or not, to be honest with you. But it’s familiarity with the adverse-effect profile. I really enjoyed the data that came out at this year’s SGO meeting [Gynecologic Oncology Conference]. You know, eliminating that toxicity and getting rid of the thrombocytopenia with a more—it’s worth saying again—based on the weight and the platelet count, we’re able to eliminate that with the 200-mg dose. So it’s meaningful.

Bradley J. Monk, MD, FACOG, FACS: So we have 3 things. You have mentioned activity, toxicity, and familiarity. How about convenience? You know rucaparib and olaparib are twice daily. Niraparib in once daily. Is there a story there?

Elena S. Ratner, MD: Yeah, I think there is. I think maintenance and treatment are different timelines in patients’ lives. I think women in the maintenance setting do not accept as much in terms of adverse effects or inconvenience as they will in treatment. Even though we all know it’s truly treatment, that’s not for them in the point of the treatment life. I think that once-a-day is convenient. I think that “weights and plates” changed how women tolerate it. So I think in the maintenance setting it has to be something that has a low adverse-effect profile and is convenient—doesn’t disturb their life. But again, to me it comes down to this personalized treatment. In somebody who has metastatic disease, I will use niraparib because I see data about crossing the blood-brain barrier with niraparib. In other women who have the baseline and lower platelets, and I know have had trouble before with thrombocytopenia, I won’t. But I also, just like Brian, believe in PARP after PARP after PARP. So all my women have been on all 3 PARPs, maybe even 6 times.

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

Elena S. Ratner, MD: Right.

Bradley J. Monk, MD, FACOG, FACS: So activity, toxicity, familiarity, convenience. At this year’s SGO, we had a whole session on cost and financial toxicity. Katie, how much does the cost of the 3 different PARP inhibitors play into the decision-making process?

Kathleen N. Moore, MD: To be perfectly honest, for me, right now, it does not come into play really because it’s just not…I know people are going to shoot daggers at me, but I want women to live longer, and it costs what it costs. I’m here to take care of patients, and I want them to have the best drugs. And truthfully, between the 3 PARP inhibitors—and I use all 3 as well—the patient assistance programs are so robust that…

Bradley J. Monk, MD, FACOG, FACS: You think they’re the same?

Kathleen N. Moore, MD: I think that they’re different, but they’ve all been accommodating to all my patients. I haven’t had a single patient who couldn’t get a PARP. I live in Oklahoma, where I don’t have a lot of patients who can walk in with cash. They just are kind of hardworking folks who can’t even afford a $200 co-pay. It’s too much money. And they can get this drug. We have financial teams, and I have resources that I know a lot of oncologists don’t have because I’m at a cancer center. We have financial navigators who help get them to that point. But we’ve been able to successfully, even for our patients with state insurance, get PARPs.

Bradley J. Monk, MD, FACOG, FACS: Brian, how inappropriate would it be, as you walk out of the room with the patient who responded second line who needs PARP maintenance—because she says it’s virtually unethical, at least not to talk about it—to tell your nurse practitioner or PA [physician assistant] or whomever, “Just give her the 1 that has the lowest co-pay”? Because she admitted they’re the same, and I don’t think they are the same either. What would be wrong with that approach?

Brian M. Slomovitz, MD: I love this conversation. This is the first time in gynecologic oncology that we’ve had 3 drugs with the same class approved. Normally, we used to think about the class efficacy, and we don’t have to worry about this problem. So now we’re like a cardiologist worrying about which antihypertensive medicine to give. We have a whole plethora to choose from. So I love the fact that we’re having this conversation.

I would really, you know, complement the 3 PARPs that are approved. The patient-assistance programs for all 3 of them have really, in my experience, been wonderful and have helped patients, when we choose a drug, get the drug. So I’m not choosing 1 or the other. All 3 of them are great. So truthfully, Brad, I’ve never had that problem—which 1 has the higher co-pay or not. And while the nurse practitioners are helping the patient get the 1 that we’re prescribing, they’re not coming back with that issue.

Bradley J. Monk, MD, FACOG, FACS: Elena, what are your comments on cost?

Elena S. Ratner, MD: Similar. Just [as] Katie said, I believe in it from the society perspective, but I think at this point it’s such an advantage that we have had for the first time, really in a long time, in improving women’s lives. It’s vital. I don’t think there’s a question.

Transcript Edited for Clarity

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Transcript: 

Bradley J. Monk, MD, FACOG, FACS: Katie, the second elephant in the room is: Which PARP [poly (ADP-ribose) polymerase]? It’s unprecedented that we have medications with virtually identical labels. We have olaparib, rucaparib, and niraparib for patients who respond to second-line platinum. Tell me the things you consider in choosing 1 PARP inhibitor over another. And I apologize for putting you on the spot, but that’s what these guys want to know.

Kathleen N. Moore, MD: What do you think about when you’re choosing a medication? You think about efficacy; you think about adverse effects. What we know, again, from a lot of data across all 3 PARP inhibitors is that these are all very good drugs. There’s not, of the 3 of them, a best PARP and a least-best PARP. They all work, as best as we can tell, equally well. When you look at the BRCA hazard ratios for maintenance and for rucaparib—and actually all 3 of them now; the QUADRA data will be out soon—and the BRCA response rates in treatment, the maintenance hazard ratios are almost identical. If you look at HRD [homologous recombination deficiency]–positive in the maintenance, they’re almost identical.

The efficacy of all 3 of them is very, very similar across treatment lines. I don’t really think you can pick based on that. Prior to the “weights and plates” [body weights and platelets] analysis, the RADAR analysis with niraparib—which was a response to the high prevalence of thrombocytopenia in NOVA—I think that was sort of a way to discriminate on an adverse-event standpoint among the 3 PARP inhibitors because the other 2 didn’t have that high-grade toxicity. You presented the PRIMA data, which is frontline with that modification in from the beginning, not a reaction to the platelets. From the beginning, we individualized dosing and have demonstrated that the hematologic toxicities look really—again, if you compare with SOLO-1, which is the other frontline—identical.

I don’t know that you can discriminate them based on key adverse events. There are some differences. Niraparib has some hypertension and thrombocytopenia. Rucaparib has the transaminase elevation. There’s some anemia with SOLO-1. But none of them really kind of make you pick 1 over the other. It honestly comes down to what you’re comfortable with. So if you are comfortable with olaparib, use olaparib. If you’re comfortable with niraparib, use niraparib because that’s what’s going to help your patients stay on longer—your familiarity and your ability to set expectations, manage adverse effects, and help her feel comfortable that she’s on the right medication. You’re kind of guessing between the 3 PARPs.

Bradley J. Monk, MD, FACOG, FACS: So lots of talking points. You said activity and toxicity, and then you said that the most common dose of niraparib was 200 [mg], and you can get there faster by starting at 200 [mg] if the patient weighs less than 77 kg. Or you have got to have both—a baseline platelet count of 150 [x 109 L].

Kathleen N. Moore, MD: Right.

Bradley J. Monk, MD, FACOG, FACS: And once you personalized proactively the dose, then the toxicities are more similar. And then you said activity. And then you added a third: familiarity. There are others.

Kathleen N. Moore, MD: That’s true.

Bradley J. Monk, MD, FACOG, FACS: Brian, what do you think about this idea that in the non-BRCA patients, which is most patients, niraparib is more lipophilic and has higher intratumoral concentrations, and that’s why it’s once daily. And that NOVA was the only trial really to isolate the treatment effect in the non-BRCA cohort. Does that resonate with you? Is there a story there? I’m not asking you whether niraparib is your choice, but is there a story there?

Brian M. Slomovitz, MD: As far as my choice, I use all 3, based on the indications that they’re approved for. As far as the niraparib data, maybe it is broader in all comers, and you may allow for the BRCA wild type. I will use it, perhaps, in there more in that setting. But I’m not sure of the right answer. I’m not sure if it’s the lipophilic absorption within the cell or not, to be honest with you. But it’s familiarity with the adverse-effect profile. I really enjoyed the data that came out at this year’s SGO meeting [Gynecologic Oncology Conference]. You know, eliminating that toxicity and getting rid of the thrombocytopenia with a more—it’s worth saying again—based on the weight and the platelet count, we’re able to eliminate that with the 200-mg dose. So it’s meaningful.

Bradley J. Monk, MD, FACOG, FACS: So we have 3 things. You have mentioned activity, toxicity, and familiarity. How about convenience? You know rucaparib and olaparib are twice daily. Niraparib in once daily. Is there a story there?

Elena S. Ratner, MD: Yeah, I think there is. I think maintenance and treatment are different timelines in patients’ lives. I think women in the maintenance setting do not accept as much in terms of adverse effects or inconvenience as they will in treatment. Even though we all know it’s truly treatment, that’s not for them in the point of the treatment life. I think that once-a-day is convenient. I think that “weights and plates” changed how women tolerate it. So I think in the maintenance setting it has to be something that has a low adverse-effect profile and is convenient—doesn’t disturb their life. But again, to me it comes down to this personalized treatment. In somebody who has metastatic disease, I will use niraparib because I see data about crossing the blood-brain barrier with niraparib. In other women who have the baseline and lower platelets, and I know have had trouble before with thrombocytopenia, I won’t. But I also, just like Brian, believe in PARP after PARP after PARP. So all my women have been on all 3 PARPs, maybe even 6 times.

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

Elena S. Ratner, MD: Right.

Bradley J. Monk, MD, FACOG, FACS: So activity, toxicity, familiarity, convenience. At this year’s SGO, we had a whole session on cost and financial toxicity. Katie, how much does the cost of the 3 different PARP inhibitors play into the decision-making process?

Kathleen N. Moore, MD: To be perfectly honest, for me, right now, it does not come into play really because it’s just not…I know people are going to shoot daggers at me, but I want women to live longer, and it costs what it costs. I’m here to take care of patients, and I want them to have the best drugs. And truthfully, between the 3 PARP inhibitors—and I use all 3 as well—the patient assistance programs are so robust that…

Bradley J. Monk, MD, FACOG, FACS: You think they’re the same?

Kathleen N. Moore, MD: I think that they’re different, but they’ve all been accommodating to all my patients. I haven’t had a single patient who couldn’t get a PARP. I live in Oklahoma, where I don’t have a lot of patients who can walk in with cash. They just are kind of hardworking folks who can’t even afford a $200 co-pay. It’s too much money. And they can get this drug. We have financial teams, and I have resources that I know a lot of oncologists don’t have because I’m at a cancer center. We have financial navigators who help get them to that point. But we’ve been able to successfully, even for our patients with state insurance, get PARPs.

Bradley J. Monk, MD, FACOG, FACS: Brian, how inappropriate would it be, as you walk out of the room with the patient who responded second line who needs PARP maintenance—because she says it’s virtually unethical, at least not to talk about it—to tell your nurse practitioner or PA [physician assistant] or whomever, “Just give her the 1 that has the lowest co-pay”? Because she admitted they’re the same, and I don’t think they are the same either. What would be wrong with that approach?

Brian M. Slomovitz, MD: I love this conversation. This is the first time in gynecologic oncology that we’ve had 3 drugs with the same class approved. Normally, we used to think about the class efficacy, and we don’t have to worry about this problem. So now we’re like a cardiologist worrying about which antihypertensive medicine to give. We have a whole plethora to choose from. So I love the fact that we’re having this conversation.

I would really, you know, complement the 3 PARPs that are approved. The patient-assistance programs for all 3 of them have really, in my experience, been wonderful and have helped patients, when we choose a drug, get the drug. So I’m not choosing 1 or the other. All 3 of them are great. So truthfully, Brad, I’ve never had that problem—which 1 has the higher co-pay or not. And while the nurse practitioners are helping the patient get the 1 that we’re prescribing, they’re not coming back with that issue.

Bradley J. Monk, MD, FACOG, FACS: Elena, what are your comments on cost?

Elena S. Ratner, MD: Similar. Just [as] Katie said, I believe in it from the society perspective, but I think at this point it’s such an advantage that we have had for the first time, really in a long time, in improving women’s lives. It’s vital. I don’t think there’s a question.

Transcript Edited for Clarity
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