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Upfront Antiangiogenic Therapy in Advanced Ovarian Cancer

Panelists: Bradley J. Monk, MD, University of Arizona and Creighton University; Robert L. Coleman, MD, MD Anderson Cancer Center; Gottfried E. Konecny, MD, University of California, Los Angeles; Katie Moore, MD, University of Oklahoma; Matthew A. Powell, MD, Washington University in St. Louis
Published: Thursday, Jul 27, 2017



Transcript:

Bradley J. Monk, MD: The upfront use of bevacizumab was also studied. You mentioned that you do dose-dense weekly therapy when you’re trying to have maximum site-cell kill prior to interval debulking. That’s what they did here. They had a randomized phase II trial, chemotherapy with or without bevacizumab, to try to make the surgery easier. I don’t know if anybody wants to make a comment on that.

Katie Moore, MD: It worked. It’s a phase II trial, but it looked like it worked. That’s what we expected.

Bradley J. Monk, MD: It was pretty tolerable. I was surprised. We always wondered if, because of the antiangiogenesis effect, there might be more surgical complications in preinterval debulking with bevacizumab during those 3 cycles, and there wasn’t.

Matthew A. Powell, MD: You mean that it was safe?

Bradley J. Monk, MD: Yes.

Matthew A. Powell, MD: Because the outcomes are still looking quite similar, the complete microscopic response rate was essentially the same, no differences.

Gottfried E. Konecny, MD: I was actually disappointed because when you take the recurrent setting and platinum resistant disease, the addition of bevacizumab increases the response rate. So, I was thinking, “Well, maybe in the neoadjuvant setting, you would see a higher pathological complete response rate,” which was similar between both settings. Look at the breast cancer data: when you add Avastin [bevacizumab] to standard neoadjuvant chemotherapy, there is a subgroup where the PCR rate significantly increases—the triple-negative patients. I thought it’s maybe too small of a study to really make a definite conclusion on it.

Bradley J. Monk, MD: There was no increase in pathologic CRs.

Matthew A. Powell, MD: They’re including improving surgical outcomes as one of their secondary endpoints; that it did seem to make the surgeries easier.

Katie Moore, MD: Right, that’s what I’m saying. If you leave someone with disease at interval cytoreduction, that someone is not going to do very well, and so it actually did meet that endpoint. We don’t have survival outcomes, but…

Matthew A. Powell, MD: And the PFS was the same in the 2 groups at this point.

Robert L. Coleman, MD: And I think, to Brad’s point with the safety, we have used the experience of our colleagues about the half-life of bevacizumab. So, we stop it, then cycle it; a full cycle ahead, and we start a full cycle after. We’ve done this in our other trials, GOG-262 for instance. So, I think it reaffirms the safety from that approach.

Bradley J. Monk, MD: One of the concepts after surgery is chemotherapy, without HIPEC or IP, as maintenance. At the Society of Gynecologic Oncology, there was a study that took 11 years to do, called GOG-212, about this idea of giving maintenance paclitaxel. It was a 3-arm study: first arm, no maintenance; second arm, maintenance for a year with paclitaxel at 135 mg/m2; and then the third arm, a new taxane analog. It was, again, definitively negative, like GOG-252. Do you guys use maintenance treatment in your practice at all?

Several: No.

Matthew A. Powell, MD: Not taxanes.

Bradley J. Monk, MD: What would you use as frontline maintenance?

Matthew A. Powell, MD: I think, at this point, I would still be compelled by some of the data on bevacizumab, although the availability is still tricky. I still think you have to look at the ICON trial results and GOG-218 and ask, “Is there a role for it in certain patient populations?” I certainly see it being used. But again, it’s not in our NCCN Guidelines yet in the United States.

Bradley J. Monk, MD: The challenge is that it’s not FDA-approved, but there’s still some uptake. So, when you use frontline, it’s bevacizumab with chemotherapy and then bevacizumab maintenance for a total of 15 months.

Robert L. Coleman, MD: Around the world, but there’s no doubt that none of us feel comfortable with that first complete remission. We know that patients have a very high rate of recurrence and that’s been driving all the research that has looked at, what are we doing in maintenance?

Gottfried E. Konecny, MD: We’re not going to get better data. It confirms Maurie Markman’s studies in the early 2000s, that giving more of the same treatment after 6 cycles is not going to improve survival.

Bradley J. Monk, MD: Tell us about the clinical trials then, generally, with a PARP inhibitor in maintenance.

Gottfried E. Konecny, MD: Well, that’s a very different story. In that case, you’re using a targeted therapy in a setting of patients with either germline mutations or excluded platinum sensitivity. And as you know well, there are 2 presentations at ASCO this year regarding the efficacy of olaparib in platinum-sensitive disease, initially presented at the SGO Annual Meeting, and a very nice quality of life. So, we got a patient reported outcomes update on this study.

Bradley J. Monk, MD: Let’s save that, because that’s a recurrent disease. This is frontline maintenance. SOLO-1 is a BRCA germline mutation, phase III frontline maintenance trial. It’s enrolled, and we’re waiting. There’s another trial for adding PARP inhibitors to frontline bevacizumab in maintenance called PAOLA-1. That’s going to close enrollment very soon. And then there’s the PRIMA study with niraparib with all-comers, but it’s focused on the HRD subsets. So, we have these 3 frontline maintenance trials that are going to be really, really interesting. We need your help, obviously, particularly with the PRIMA study, frontline niraparib.

Robert L. Coleman, MD: The only one I would add to that is GOG-3005, which brings another PARP inhibitor.

Katie Moore, MD: And we have 3 I-Os in maintenance.

Bradley J. Monk, MD: That’s right. The difference with GOG-3005’s PARP inhibitor, veliparib, is that it begins with chemotherapy/PARP inhibition and then moves to PARP inhibitor maintenance. So, the other PARPs begin, switch maintenance after chemotherapy.

Robert L. Coleman, MD: Correct.

Bradley J. Monk, MD: We’ll get to I-Os, but I-O maintenance is really another question, and there are 2 frontline I-O maintenance trials: one with avelumab and one with atezolizumab. And with atezolizumab, because it’s made by the people who make bevacizumab, there’s a bevacizumab/atezolizumab combination.

Robert L. Coleman, MD: So, it’s a combination maintenance.

Bradley J. Monk, MD: Very compelling.

Transcript Edited for Clarity

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Transcript:

Bradley J. Monk, MD: The upfront use of bevacizumab was also studied. You mentioned that you do dose-dense weekly therapy when you’re trying to have maximum site-cell kill prior to interval debulking. That’s what they did here. They had a randomized phase II trial, chemotherapy with or without bevacizumab, to try to make the surgery easier. I don’t know if anybody wants to make a comment on that.

Katie Moore, MD: It worked. It’s a phase II trial, but it looked like it worked. That’s what we expected.

Bradley J. Monk, MD: It was pretty tolerable. I was surprised. We always wondered if, because of the antiangiogenesis effect, there might be more surgical complications in preinterval debulking with bevacizumab during those 3 cycles, and there wasn’t.

Matthew A. Powell, MD: You mean that it was safe?

Bradley J. Monk, MD: Yes.

Matthew A. Powell, MD: Because the outcomes are still looking quite similar, the complete microscopic response rate was essentially the same, no differences.

Gottfried E. Konecny, MD: I was actually disappointed because when you take the recurrent setting and platinum resistant disease, the addition of bevacizumab increases the response rate. So, I was thinking, “Well, maybe in the neoadjuvant setting, you would see a higher pathological complete response rate,” which was similar between both settings. Look at the breast cancer data: when you add Avastin [bevacizumab] to standard neoadjuvant chemotherapy, there is a subgroup where the PCR rate significantly increases—the triple-negative patients. I thought it’s maybe too small of a study to really make a definite conclusion on it.

Bradley J. Monk, MD: There was no increase in pathologic CRs.

Matthew A. Powell, MD: They’re including improving surgical outcomes as one of their secondary endpoints; that it did seem to make the surgeries easier.

Katie Moore, MD: Right, that’s what I’m saying. If you leave someone with disease at interval cytoreduction, that someone is not going to do very well, and so it actually did meet that endpoint. We don’t have survival outcomes, but…

Matthew A. Powell, MD: And the PFS was the same in the 2 groups at this point.

Robert L. Coleman, MD: And I think, to Brad’s point with the safety, we have used the experience of our colleagues about the half-life of bevacizumab. So, we stop it, then cycle it; a full cycle ahead, and we start a full cycle after. We’ve done this in our other trials, GOG-262 for instance. So, I think it reaffirms the safety from that approach.

Bradley J. Monk, MD: One of the concepts after surgery is chemotherapy, without HIPEC or IP, as maintenance. At the Society of Gynecologic Oncology, there was a study that took 11 years to do, called GOG-212, about this idea of giving maintenance paclitaxel. It was a 3-arm study: first arm, no maintenance; second arm, maintenance for a year with paclitaxel at 135 mg/m2; and then the third arm, a new taxane analog. It was, again, definitively negative, like GOG-252. Do you guys use maintenance treatment in your practice at all?

Several: No.

Matthew A. Powell, MD: Not taxanes.

Bradley J. Monk, MD: What would you use as frontline maintenance?

Matthew A. Powell, MD: I think, at this point, I would still be compelled by some of the data on bevacizumab, although the availability is still tricky. I still think you have to look at the ICON trial results and GOG-218 and ask, “Is there a role for it in certain patient populations?” I certainly see it being used. But again, it’s not in our NCCN Guidelines yet in the United States.

Bradley J. Monk, MD: The challenge is that it’s not FDA-approved, but there’s still some uptake. So, when you use frontline, it’s bevacizumab with chemotherapy and then bevacizumab maintenance for a total of 15 months.

Robert L. Coleman, MD: Around the world, but there’s no doubt that none of us feel comfortable with that first complete remission. We know that patients have a very high rate of recurrence and that’s been driving all the research that has looked at, what are we doing in maintenance?

Gottfried E. Konecny, MD: We’re not going to get better data. It confirms Maurie Markman’s studies in the early 2000s, that giving more of the same treatment after 6 cycles is not going to improve survival.

Bradley J. Monk, MD: Tell us about the clinical trials then, generally, with a PARP inhibitor in maintenance.

Gottfried E. Konecny, MD: Well, that’s a very different story. In that case, you’re using a targeted therapy in a setting of patients with either germline mutations or excluded platinum sensitivity. And as you know well, there are 2 presentations at ASCO this year regarding the efficacy of olaparib in platinum-sensitive disease, initially presented at the SGO Annual Meeting, and a very nice quality of life. So, we got a patient reported outcomes update on this study.

Bradley J. Monk, MD: Let’s save that, because that’s a recurrent disease. This is frontline maintenance. SOLO-1 is a BRCA germline mutation, phase III frontline maintenance trial. It’s enrolled, and we’re waiting. There’s another trial for adding PARP inhibitors to frontline bevacizumab in maintenance called PAOLA-1. That’s going to close enrollment very soon. And then there’s the PRIMA study with niraparib with all-comers, but it’s focused on the HRD subsets. So, we have these 3 frontline maintenance trials that are going to be really, really interesting. We need your help, obviously, particularly with the PRIMA study, frontline niraparib.

Robert L. Coleman, MD: The only one I would add to that is GOG-3005, which brings another PARP inhibitor.

Katie Moore, MD: And we have 3 I-Os in maintenance.

Bradley J. Monk, MD: That’s right. The difference with GOG-3005’s PARP inhibitor, veliparib, is that it begins with chemotherapy/PARP inhibition and then moves to PARP inhibitor maintenance. So, the other PARPs begin, switch maintenance after chemotherapy.

Robert L. Coleman, MD: Correct.

Bradley J. Monk, MD: We’ll get to I-Os, but I-O maintenance is really another question, and there are 2 frontline I-O maintenance trials: one with avelumab and one with atezolizumab. And with atezolizumab, because it’s made by the people who make bevacizumab, there’s a bevacizumab/atezolizumab combination.

Robert L. Coleman, MD: So, it’s a combination maintenance.

Bradley J. Monk, MD: Very compelling.

Transcript Edited for Clarity
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Online CME Activities
TitleExpiration DateCME Credits
Oncology Best Practice™: Expert Perspectives to Incorporate Evidence on PARP Inhibitors into Practice and Optimize the Medical Management of Ovarian CancerOct 31, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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