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Systemic Therapy Selection for Advanced EOC

Panelists: Bradley Monk, MD, FACOG, FACS, St. Joseph's Hospital and Medical Center; Michael J. Birrer, MD, PhD, O'Neal Comprehensive Cancer Center; Jubilee Brown, MD, Levine Cancer Institute; Thomas Herzog, MD, UC College of Medicine; Krishnansu S. Tewari, MD, University of California, Irvine
Published: Tuesday, Jul 30, 2019



Transcript:

Bradley Monk, MD, FACOG, FACS: Greetings, and thank you for joining this OncLive® Peer Exchange® entitled “Recent Developments in Management of Gynecologic Cancers.”

With the development of new therapies for gynecologic malignancies, questions arise regarding how to optimally incorporate these treatments into the current paradigms for patients with newly diagnosed and recurrent disease.

In this OncLive® Peer Exchange®, my colleagues and I will discuss recent data surrounding new and emerging therapies for ovarian, cervical, uterine, and endometrial carcinomas and how the latest research may impact your clinical practice.

My name is Dr Brad Monk. I’m a professor in and the director of the Division of Gynecologic Oncology at Creighton University School of Medicine and the University of Arizona College of Medicine, both in Phoenix, Arizona. And I’m part of the Arizona Oncology US Oncology Network.

Participating with me today on our distinguished panel are my good friend and colleague Dr Michael Birrer, a professor and medical oncologist at the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham. Welcome, Michael.

Michael J. Birrer, MD, PhD: Glad to be here.

Bradley Monk, MD, FACOG, FACS: That’s great. And Dr Jubilee Brown, a professor and the associate director of gynecologic oncology at Atrium Health’s Levine Cancer Institute in Charlotte, North Carolina. Welcome, Jubilee.

Jubilee Brown, MD: Thanks, Brad.

Bradley Monk, MD, FACOG, FACS: And Dr Thomas Herzog, a professor of obstetrics and gynecology at the University of Cincinnati College of Medicine and the deputy director of the University of Cincinnati Cancer Institute. Welcome, Tom.

Thomas Herzog, MD: Thanks for having me, Brad.

Bradley Monk, MD, FACOG, FACS: My pleasure. And Krishnansu Tewari, a professor at and the director of the Division of Gynecologic Oncology at the University of California, Irvine, School of Medicine in Orange, California. Krish, welcome.

Krishnansu S. Tewari, MD: Thank you.

Bradley Monk, MD, FACOG, FACS: My pleasure. Thank you so much for joining us. Let’s begin. It’s finally time to change how we treat newly diagnosed advanced ovarian cancer. It prevents the biggest and most important opportunity to change long-term outcomes. One of the evolving paradigms I think that all of us accept is intraperitoneal IP chemotherapy. We’ve been thinking about this and talking about this for many years. Finally, I think, our definitive randomized phase III trial of 1500 patients was just published. Tom—in the Journal of Clinical Oncology—tell me about GOG-0252.

Thomas Herzog, MD: Well, Brad, I think that you sort of have to set the scene a little bit as to what the interest has been in terms of data for advocating intraperitoneal therapies. You had 3 randomized phase III trials that have looked at incorporating IP chemotherapy]: GOG-104, GOG-114, and GOG-172. And each of those showed an improvement in either progression-free survival [PFS] and/or overall survival [OS] by about 20% to 30%, so hazard ratios of 0.7 to 0.8. People were moved by that data, and that of course was in patients who were optimally cytoreduced, the feeling being that the less disease that was present, the more the benefit from intraperitoneal chemotherapy.

What’s interesting is there’s been a low uptake for IP chemotherapy even with 3 phase III trials by the NCI [National Cancer Institute]; people were not using it. There are concerns about toxicity, and there are concerns about how these trials were conducted. Is it just because you’re getting more drug? And so in an effort to try to isolate the effect of intraperitoneal chemotherapy, some of the biggest enthusiasts of intraperitoneal chemotherapy—Joan Walker, Deborah Armstrong, and colleagues designed this trial—GOG 252. And it had 3 arms, 2 of which were using an intraperitoneal component, 1 with intraperitoneal carboplatin, 1 with intraperitoneal cisplatin, and then standard therapy of IV [intravenous].

What’s interesting about this particular trial—and it’s always difficult when you construct trials, because you have to figure out what the standard of care may be, or you have to do major amendments. And in this case, they thought that everyone would be getting bevacizumab. And so everyone in this trial on all 3 arms received bevacizumab. And that’s important because the few supporters of IP chemotherapy point out that that may be why there was no difference in these. If you look at the primary endpoint of PFS, it was 25 to 27 months, no statistical difference; the OS was same thing, no statistical difference. Primary endpoint again being PFS. In fact, if you look at the de facto analysis, they actually had more toxicity in the IP arms, which is no surprise to those of us who use IP chemotherapy.

Bradley Monk, MD, FACOG, FACS: So more toxic, not more active.

Thomas Herzog, MD: Correct. For most of us—I don’t know, I’d be interested to hear what the rest of the panel thinks. They say I’m probably not going to use IP chemotherapy that much or at all.

Bradley Monk, MD, FACOG, FACS: Krish, I think you were a coauthor on this trial.

Krishnansu S. Tewari, MD: Yeah.

Bradley Monk, MD, FACOG, FACS: Journal of Clinical Oncology. The definitive randomized phase III trial, or maybe not. What has been your uptake with intraperitoneal chemotherapy?

Krishnansu S. Tewari, MD: Zero.

Bradley Monk, MD, FACOG, FACS: Oh, that’s pretty definitive.

Krishnansu S. Tewari, MD: I’ve never been excited about it. The 3 trials Tom mentioned were all flawed methodologically.

Bradley Monk, MD, FACOG, FACS: Because they looked at other factors.

Krishnansu S. Tewari, MD: And the field has moved on. I mean, you’re talking about delivering chemotherapy with the same drugs that we’ve used for decades into the abdominal cavity. I don’t see it. The field has moved on. We have better targeted therapies, better options, and better opportunities to help patients. So uptake with us is 0, at least with me.

Bradley Monk, MD, FACOG, FACS: Professor Michael Birrer is a medical oncologist. We always have to have you here to balance this. In the medical oncology world, is intraperitoneal chemotherapy even talked about anymore?

Michael J. Birrer, MD, PhD: Not really. I think in this case I won’t balance you all because I’m going to be on the same side. I grew up with Robert F. Ozols and Robert C. Young, and we talked IV dose intensity. We were never a big fan of IP chemotherapy. And I think Krish is right—a lot of those studies we talk about are fundamentally flawed.

Bradley Monk, MD, FACOG, FACS: So let’s put that to rest.

Michael J. Birrer, MD, PhD: I think so.

Bradley Monk, MD, FACOG, FACS: Let’s put that to rest.

Thomas Herzog, MD: Well, it’s easy to do so. But there are—I just want to point out, and I’m not 1 of them—some prominent thought leaders, 1 of whom I know is a medical oncologist, who are still carrying the flag for IP chemotherapy, saying maybe in BRCA. And, as you said, we’ve moved on with PARP inhibitors and everything else.

Bradley Monk, MD, FACOG, FACS: So Jubilee, why are there these people who just can’t let go?
Jubilee Brown, MD: I think there is a small component of patients who—as you mentioned, Tom—are BRCA-positive and who may benefit from IP chemotherapy.

Bradley Monk, MD, FACOG, FACS: May? We’re giving them olaparib now.

Jubilee Brown, MD: Well, is there a way you can use IP chemotherapy in those patients and then proceed on to olaparib?

Bradley Monk, MD, FACOG, FACS: So you want to do another study? You want to do another 1500 patients?

Jubilee Brown, MD: Not advocating that. Not advocating that.

Bradley Monk, MD, FACOG, FACS: Tom, how about HIPEC [hyperthermic intraperitoneal chemotherapy]? There was this New England Journal of Medicine paper a year and a half ago that heated intraperitoneal chemotherapy, done at the time of interval debulking in the setting of neoadjuvant chemotherapy, given between the third and the fourth doses. Maybe that’s the secret sauce.

Thomas Herzog, MD: Yeah, it’s hard to interpret that trial. It’s a relatively small trial, first of all. And if you look at the intervention, it was just whether they got 50 of cisplatin intraperitoneally. That was the only change in the neoadjuvant setting. One course, that’s it. PFS, meh.

Bradley Monk, MD, FACOG, FACS: So 6 IP therapies didn’t work, but maybe 1 will. Is that what you’re saying?

Thomas Herzog, MD: Yeah, it’s very odd. It’s very odd.

Bradley Monk, MD, FACOG, FACS: What is it, though, a couple of degrees?

Thomas Herzog, MD: But as you said, it made the New England Journal of Medicine. I do think it deserves further follow-up in terms of other trials because we need to know what to do with that data. But the interesting thing is that PFS was modestly improved but nothing that was impressive. But the OS was.

Michael J. Birrer, MD, PhD: It had substantial toxicity?

Bradley Monk, MD, FACOG, FACS: Substantial toxicity.

Thomas Herzog, MD: Substantially improved by over a year. How that happened, I don’t know. Sure, certainly makes 1 concerned for a type 1 error.

Transcript Edited for Clarity

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Transcript:

Bradley Monk, MD, FACOG, FACS: Greetings, and thank you for joining this OncLive® Peer Exchange® entitled “Recent Developments in Management of Gynecologic Cancers.”

With the development of new therapies for gynecologic malignancies, questions arise regarding how to optimally incorporate these treatments into the current paradigms for patients with newly diagnosed and recurrent disease.

In this OncLive® Peer Exchange®, my colleagues and I will discuss recent data surrounding new and emerging therapies for ovarian, cervical, uterine, and endometrial carcinomas and how the latest research may impact your clinical practice.

My name is Dr Brad Monk. I’m a professor in and the director of the Division of Gynecologic Oncology at Creighton University School of Medicine and the University of Arizona College of Medicine, both in Phoenix, Arizona. And I’m part of the Arizona Oncology US Oncology Network.

Participating with me today on our distinguished panel are my good friend and colleague Dr Michael Birrer, a professor and medical oncologist at the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham. Welcome, Michael.

Michael J. Birrer, MD, PhD: Glad to be here.

Bradley Monk, MD, FACOG, FACS: That’s great. And Dr Jubilee Brown, a professor and the associate director of gynecologic oncology at Atrium Health’s Levine Cancer Institute in Charlotte, North Carolina. Welcome, Jubilee.

Jubilee Brown, MD: Thanks, Brad.

Bradley Monk, MD, FACOG, FACS: And Dr Thomas Herzog, a professor of obstetrics and gynecology at the University of Cincinnati College of Medicine and the deputy director of the University of Cincinnati Cancer Institute. Welcome, Tom.

Thomas Herzog, MD: Thanks for having me, Brad.

Bradley Monk, MD, FACOG, FACS: My pleasure. And Krishnansu Tewari, a professor at and the director of the Division of Gynecologic Oncology at the University of California, Irvine, School of Medicine in Orange, California. Krish, welcome.

Krishnansu S. Tewari, MD: Thank you.

Bradley Monk, MD, FACOG, FACS: My pleasure. Thank you so much for joining us. Let’s begin. It’s finally time to change how we treat newly diagnosed advanced ovarian cancer. It prevents the biggest and most important opportunity to change long-term outcomes. One of the evolving paradigms I think that all of us accept is intraperitoneal IP chemotherapy. We’ve been thinking about this and talking about this for many years. Finally, I think, our definitive randomized phase III trial of 1500 patients was just published. Tom—in the Journal of Clinical Oncology—tell me about GOG-0252.

Thomas Herzog, MD: Well, Brad, I think that you sort of have to set the scene a little bit as to what the interest has been in terms of data for advocating intraperitoneal therapies. You had 3 randomized phase III trials that have looked at incorporating IP chemotherapy]: GOG-104, GOG-114, and GOG-172. And each of those showed an improvement in either progression-free survival [PFS] and/or overall survival [OS] by about 20% to 30%, so hazard ratios of 0.7 to 0.8. People were moved by that data, and that of course was in patients who were optimally cytoreduced, the feeling being that the less disease that was present, the more the benefit from intraperitoneal chemotherapy.

What’s interesting is there’s been a low uptake for IP chemotherapy even with 3 phase III trials by the NCI [National Cancer Institute]; people were not using it. There are concerns about toxicity, and there are concerns about how these trials were conducted. Is it just because you’re getting more drug? And so in an effort to try to isolate the effect of intraperitoneal chemotherapy, some of the biggest enthusiasts of intraperitoneal chemotherapy—Joan Walker, Deborah Armstrong, and colleagues designed this trial—GOG 252. And it had 3 arms, 2 of which were using an intraperitoneal component, 1 with intraperitoneal carboplatin, 1 with intraperitoneal cisplatin, and then standard therapy of IV [intravenous].

What’s interesting about this particular trial—and it’s always difficult when you construct trials, because you have to figure out what the standard of care may be, or you have to do major amendments. And in this case, they thought that everyone would be getting bevacizumab. And so everyone in this trial on all 3 arms received bevacizumab. And that’s important because the few supporters of IP chemotherapy point out that that may be why there was no difference in these. If you look at the primary endpoint of PFS, it was 25 to 27 months, no statistical difference; the OS was same thing, no statistical difference. Primary endpoint again being PFS. In fact, if you look at the de facto analysis, they actually had more toxicity in the IP arms, which is no surprise to those of us who use IP chemotherapy.

Bradley Monk, MD, FACOG, FACS: So more toxic, not more active.

Thomas Herzog, MD: Correct. For most of us—I don’t know, I’d be interested to hear what the rest of the panel thinks. They say I’m probably not going to use IP chemotherapy that much or at all.

Bradley Monk, MD, FACOG, FACS: Krish, I think you were a coauthor on this trial.

Krishnansu S. Tewari, MD: Yeah.

Bradley Monk, MD, FACOG, FACS: Journal of Clinical Oncology. The definitive randomized phase III trial, or maybe not. What has been your uptake with intraperitoneal chemotherapy?

Krishnansu S. Tewari, MD: Zero.

Bradley Monk, MD, FACOG, FACS: Oh, that’s pretty definitive.

Krishnansu S. Tewari, MD: I’ve never been excited about it. The 3 trials Tom mentioned were all flawed methodologically.

Bradley Monk, MD, FACOG, FACS: Because they looked at other factors.

Krishnansu S. Tewari, MD: And the field has moved on. I mean, you’re talking about delivering chemotherapy with the same drugs that we’ve used for decades into the abdominal cavity. I don’t see it. The field has moved on. We have better targeted therapies, better options, and better opportunities to help patients. So uptake with us is 0, at least with me.

Bradley Monk, MD, FACOG, FACS: Professor Michael Birrer is a medical oncologist. We always have to have you here to balance this. In the medical oncology world, is intraperitoneal chemotherapy even talked about anymore?

Michael J. Birrer, MD, PhD: Not really. I think in this case I won’t balance you all because I’m going to be on the same side. I grew up with Robert F. Ozols and Robert C. Young, and we talked IV dose intensity. We were never a big fan of IP chemotherapy. And I think Krish is right—a lot of those studies we talk about are fundamentally flawed.

Bradley Monk, MD, FACOG, FACS: So let’s put that to rest.

Michael J. Birrer, MD, PhD: I think so.

Bradley Monk, MD, FACOG, FACS: Let’s put that to rest.

Thomas Herzog, MD: Well, it’s easy to do so. But there are—I just want to point out, and I’m not 1 of them—some prominent thought leaders, 1 of whom I know is a medical oncologist, who are still carrying the flag for IP chemotherapy, saying maybe in BRCA. And, as you said, we’ve moved on with PARP inhibitors and everything else.

Bradley Monk, MD, FACOG, FACS: So Jubilee, why are there these people who just can’t let go?
Jubilee Brown, MD: I think there is a small component of patients who—as you mentioned, Tom—are BRCA-positive and who may benefit from IP chemotherapy.

Bradley Monk, MD, FACOG, FACS: May? We’re giving them olaparib now.

Jubilee Brown, MD: Well, is there a way you can use IP chemotherapy in those patients and then proceed on to olaparib?

Bradley Monk, MD, FACOG, FACS: So you want to do another study? You want to do another 1500 patients?

Jubilee Brown, MD: Not advocating that. Not advocating that.

Bradley Monk, MD, FACOG, FACS: Tom, how about HIPEC [hyperthermic intraperitoneal chemotherapy]? There was this New England Journal of Medicine paper a year and a half ago that heated intraperitoneal chemotherapy, done at the time of interval debulking in the setting of neoadjuvant chemotherapy, given between the third and the fourth doses. Maybe that’s the secret sauce.

Thomas Herzog, MD: Yeah, it’s hard to interpret that trial. It’s a relatively small trial, first of all. And if you look at the intervention, it was just whether they got 50 of cisplatin intraperitoneally. That was the only change in the neoadjuvant setting. One course, that’s it. PFS, meh.

Bradley Monk, MD, FACOG, FACS: So 6 IP therapies didn’t work, but maybe 1 will. Is that what you’re saying?

Thomas Herzog, MD: Yeah, it’s very odd. It’s very odd.

Bradley Monk, MD, FACOG, FACS: What is it, though, a couple of degrees?

Thomas Herzog, MD: But as you said, it made the New England Journal of Medicine. I do think it deserves further follow-up in terms of other trials because we need to know what to do with that data. But the interesting thing is that PFS was modestly improved but nothing that was impressive. But the OS was.

Michael J. Birrer, MD, PhD: It had substantial toxicity?

Bradley Monk, MD, FACOG, FACS: Substantial toxicity.

Thomas Herzog, MD: Substantially improved by over a year. How that happened, I don’t know. Sure, certainly makes 1 concerned for a type 1 error.

Transcript Edited for Clarity
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