Secondary Debulking in Recurrent Ovarian Cancer

Transcript:

Bradley J. Monk, MD: Let’s discuss recurrent ovarian cancer: histologic subtype, with mucinous clear-cell and low-grade serous disease being unique; platinum-free interval; number of lines of therapy; molecular signature; and the existing toxicities from the prior lines. That’s probably what a consult would say, right?

Katie Moore, MD: And resectability.

Bradley J. Monk, MD: Thank you. So, there was—let’s do it, at resectability—a prospective phase III trial of secondary debulking at this meeting. Rob, you have a big knife. Tell me about what’s called the DESKTOP study.

Robert L. Coleman, MD: I have to give you credit, because the DESKTOP studies are a series of trials that have been done in sequence to try to help us identify patients and the merit of doing secondary debulking. There’s no doubt about it, 3 of the 4 of us are surgeons here. We look at that disease. You said you would cut out all of the low-grade disease. So, we want to do it because we did the first time and it worked. We took it out, gave patients chemotherapy, and they did better. There has been a lot of bias to that.

The DESKTOP trials were helping us to find out, first of all, was this prognostic if we could do it? Could we find a subcohort of patients, for instance, who had good surgical outcomes the first time, no ascites and good performance status? And if you picked those patients, was it likely you could get them to R0? Because all the retrospective studies—and there are probably 3 dozen, maybe 4 dozen studies out there—have shown that that’s the case.

So, the DESKTOP 3 trial was actually set up by DESKTOP 1/2 to find the patients, the best patients, and to see if the surgery worked. And basically, the primary endpoint of that trial and the other one that’s ongoing, GOG-213, was overall survival. So, it was a little bit of a surprise.

Bradley J. Monk, MD: Because they presented PFS. They presented the secondary endpoint before the primary endpoint.

Robert L. Coleman, MD: And so, I think a lot of us feel that a PFS endpoint for a situation like this would obviously be impacted if you cut out the disease as opposed to not. But, again, the real endpoint here is overall survival. And we’re cherry-picking the most operable patients, who are also the most chemotherapy sensitive.

Bradley J. Monk, MD: There’s nothing wrong with picking the right patient to operate on.

Robert L. Coleman, MD: No, no, what I’m saying is they’re also the right patient for chemotherapy.

Gottfried E. Konecny, MD: Despite the weaknesses that you point out—that they’re reporting PFS before OS, which was the primary endpoint—I think it’s worthwhile reporting, because it could have been the other way around. We could have had no improvement in PFS, meaning that, basically, systemic progression would have taken over, even despite chasing it locally with surgery. So, I think selecting the right patients and indications is key. We already knew that. It’s really confirming what we’re doing, anyway, right now: that we are doing secondary debulking.

Bradley J. Monk, MD: Well, we’ll see, because in the setting of no randomized mature data, did this change your practice, Matt, a secondary debulking?

Matthew A. Powell, MD: I would say it was in line with my practice to begin with, that I was quite selective with who I reoperated on. I know there are some centers in the country that will reoperate on almost everybody, because nobody is as good a surgeon as they are.

Bradley J. Monk, MD: Bigger knife.

Matthew A. Powell, MD: Bigger knife, as you said. But the time to first subsequent therapy that they looked at in this trial was 7 months longer in the patients whom they operated on and got adjuvant chemotherapy afterwards. It was 7 months later before they had to start the next regimen as compared to the group that didn’t undergo surgery.

Gottfried E. Konecny, MD: You base your decision on secondary debulking on different criteria, right? They used the so-called AGO criteria that they defined in DESKTOP 1 and 2, which, if I’m correct, was no ascites or less than 500 mL, optimal debulking at the initial surgeries…

Several: Complete resection.

Bradley J. Monk, MD: We don’t do that.

Robert L. Coleman, MD: And good performance status.

Matthew A. Powell, MD: But I would say, I somewhat do those things. If it was carcinomatosis to begin with, it’s probably going to be carcinomatosis now.

Katie Moore, MD: If you couldn’t get it out the first time, you’re not going to get it out the second time.

Robert L. Coleman, MD: So, that does bring up one really important finding from the study, on the positive side of things. There has been this thought that, with the same thing in frontline therapy, there’s an incremental benefit with more that you take out. In other words, if you leave a lot, they don’t do so well. If you leave nothing, they do really well. And there’s something in-between. And so, what was showed in this study, which has also been previously reported, was that it’s really only the R0 patients who benefit. So, the criteria to maximize the R0 patients, that was the key. And they proved that they could do it.

Transcript Edited for Clarity