Therapeutic Strategies in Advanced Ovarian Cancer - Episode 10
Bradley J. Monk, MD, FACS, FACOG: Is this a practicing-changing trial, Oliver?
Oliver Dorigo, MD, PhD: Well, maybe. Tom mentioned DESKTOP III. In DESKTOP III, there were very strict criteria for selecting patients for secondary cytoreduction on not. It pertained to the amount of ascites that were present and the length of the disease-free interval. In that sense, there was a lack of bias from the provider side, or the physician side. In this trial, the progression-free survival was 5.6 months.
Bradley J. Monk, MD, FACS, FACOG: When you cut the tumor out, you’re going to change the disease-free survival. You can’t do that.
Oliver Dorigo, MD, PhD: We don’t have the overall survival data yet.
Bradley J. Monk, MD, FACS, FACOG: Right, which is the real endpoint. How could you possibly present a secondary endpoint before the primary endpoint? It’s unprecedented.
Oliver Dorigo, MD, PhD: Well, that is true. But that being said, I think that it is worthwhile to wait for the results of that trial before we say “no more secondary cytoreduction.”
Bradley J. Monk, MD, FACS, FACOG: I have publicly said that it takes 2 studies to convince you of anything. That’s when you’re doing something. But you’re already doing it with no studies. It’s the weirdest thing I’ve ever seen. It takes 2 studies to convince anyone of anything. But with no studies, you still do it. And then, when you finally get a study, which says you shouldn’t do it, people are going to continue to do it—does that make sense, Katie?
Kathleen Moore, MD: DESKTOP III did have different entry criteria. When you look at the R0 group in DESKTOP III, in particular—not just the surgery/no surgery—that progression-free survival difference is even bigger. So, you’re right. If you cut it out, you had better have a longer progression-free survival.
You don’t here in GOG-0213. They are completely discordant progression-free survival results. We didn’t have a progression-free survival difference in GOG-0213, so I’m not surprised that there’s not an overall survival difference. DESKTOP III does have a progression-free survival improvement. It’s even bigger in the R0 group. I want to see what the overall survival looks like.
Leslie M. Randall, MD, MAS: I would have suspected that GOG-0213 would be more positive than DESKTOP III. In general, we’re selecting the more oligometastatic disease and a longer platinum-free interval. I thought they were better selected.
Kathleen Moore, MD: I think it’s the reverse. In oligometastatic disease, why would I randomize them? I’m going to take that out. I’m going to randomize people in GOG-0213.
Bradley J. Monk, MD, FACS, FACOG: Oh, that’s interesting.
Kathleen Moore, MD: Why would you risk it if that’s your bias?
Bradley J. Monk, MD, FACS, FACOG: Here’s what I find most interesting…
Leslie M. Randall, MD, MAS: If you had equipoise and you still put your people on trial, which was our approach…
Kathleen Moore, MD: I’m just saying.
Leslie M. Randall, MD, MAS: That, no doubt, happens.
Bradley J. Monk, MD, FACS, FACOG: But that’s a very good point. In the patients who did not get bevacizumab post operatively, you hurt them with surgery. Not only did it not help but you hurt them. And again, it’s the hypothesis that I’ve generated—“I think I can.” When you operate on a patient, I would argue, unnecessarily, that you create a cytokine release. There’s a surge of angiogenic factors. There’s a surge in information that promotes tumor progression. So, what happens when you give postoperative bevacizumab? It calms that down. Again, it’s a small subset. You can’t draw any conclusions, but it fits with what I’ve tried to preach for many years—that ovarian cancer is a systemic disease, and chemotherapy is important. The surgery can actually hurt patients. People say, “Well, what can it hurt? I’m a great surgeon. She’s just going to spend 2 days in the hospital.” Well, I’ll tell you what it can do—it can create a cytokine surge and promote growth. Does that resonate with you, or do you think that I’m out of my mind, as usual?
Kathleen Moore, MD: I don’t think you’re out of your mind. We’re sort of making up a cloud around this confusing result that we’re all surprised about. Again, I want to see the paper with this. I want to see the results of DESKTOP III. Nobody wants to do something that shortens the life of your patient.
Bradley J. Monk, MD, FACS, FACOG: And causes suffering.
Kathleen Moore, MD: And causes suffering. The point of doing a surgery isn’t to cut someone open. That’s not the point. The point is to do something that is helping that patient live longer. If what we’re doing is not helping that patient live longer, none of us, as surgeons, are going to be real sad about stopping.
Bradley J. Monk, MD, FACS, FACOG: As I have said in other instances, we decided to do a trial. We did the trial; it was negative. If you don’t change behavior based on the results of a randomized phase III trial, I think we have a serious problem. I get it—you need to see the paper. I’m fine with that. But when the paper is published in the New England Journal of Medicine, I hope it changes practice.
Leslie M. Randall, MD, MAS: Back to your cytokine comment: I think the bigger issue is that it delays chemotherapy. Surgery delays chemotherapy. That may be the more concrete issue.
Oliver Dorigo, MD, PhD: What’s interesting about this is that we know, no doubt, that up-front interval debulking surgery as first-line treatment of ovarian cancer is necessary.
Bradley J. Monk, MD, FACS, FACOG: We have no doubt? Where’s the randomized trial that supports that?
Thomas Herzog, MD: It’s like the randomized parachute trial.
Bradley J. Monk, MD, FACS, FACOG: No, it’s not. The only randomized trial that we have of up-front surgery is GOG-152, which is 2 operations versus 1. The second operation didn’t help. So, it’s not as simple as you guys think.
Oliver Dorigo, MD, PhD: There might not be as much data, but we all do it, right? Now we have secondary cytoreduction, and it seems like it’s more of the biology of the tumor that dictates the outcome versus the surgery, right?
Leslie M. Randall, MD, MAS: That’s always the case.
Oliver Dorigo, MD, PhD: That’s always the case.
Leslie M. Randall, MD, MAS: At any point in time.
Oliver Dorigo, MD, PhD: You’re right. So, should we go back and think about what we do with patients with metastatic disease in the frontline setting? Are those patients who may respond to chemotherapy just as well as with surgery and chemotherapy? You have a patient. The patient is 89 years old and could never take the surgery. I treated her 2.5 years ago. She has a BRCA mutation, carboplatin…
Bradley J. Monk, MD, FACS, FACOG: That’s the point. You’re agreeing with me now.
Transcript Edited for Clarity