Sequencing for Treatment for Recurrent 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
Gottfried E. Konecny, MD: What would you do with a patient on maintenance? Within 8 weeks of completion of chemotherapy, you want to start a maintenance therapy. She gets the drug, but suddenly, the CA-125 bumps up.
Bradley J. Monk, MD: Good question.
Gottfried E. Konecny, MD: So, how do we define maintenance versus active treatment in that setting?
Robert L. Coleman, MD: This is treatment.
Bradley J. Monk, MD: It’s all treatment. These patients all have cancer.
Robert L. Coleman, MD: But, Brad, wait a minute. Why don’t we talk about when the decision is actually being made? The patient has platinum-sensitive recurrent disease, high-grade serous. Is your decision Taxol (paclitaxel)/carboplatin/bevacizumab because it extends overall survival, or do we go with some non-bevacizumab containing compound and then give them a treatment?
Bradley J. Monk, MD: I think we get too many variables, and I know that’s a cop-out. I’ll do all of those. In a platinum-sensitive second-line relapse, sometimes I’ll give her chemotherapy alone, but not very often. Sometimes I’ll give her carboplatin/paclitaxel/bevacizumab, and sometimes I’ll even give her a triplet with bevacizumab and then switch maintenance to niraparib, because I can always give her bevacizumab later.
Robert L. Coleman, MD: But you can’t do that all in the same patient, so you’ve got to talk about what you’re going to do.
Bradley J. Monk, MD: But there are too many different variables.
Gottfried E. Konecny, MD: But you can tailor the treatments.
Bradley J. Monk, MD: No, it’s called individualization.
Gottfried E. Konecny, MD: Molecular stratification, same point.I think if you have a BRCA mutation carrier or a high HRD score, then you prioritize the treatment.
Robert L. Coleman, MD: OK, so now he’s getting back to doing the testing.
Gottfried E. Konecny, MD: Yes.
Bradley J. Monk, MD: Well, he told us that was the first thing I talked about: How do you figure out how to treat recurrent ovarian cancer? And we agreed, number of lines of therapy, time from last platinum, molecular signature, histologic subtype, and individualization of existing toxicities. So, that’s still relevant here, and I have too many cells to say that’s my go-to regimen.
Robert L. Coleman, MD: Absolutely, and I would agree. I’m playing devil’s advocate because I want to flush out this stuff. Because most clinicians are sitting in front of the data and they’re sitting in front of a patient and they want to be doing the right thing, but they don’t have the feel of freedom to do that type of individualization that you mentioned.
Bradley J. Monk, MD: So, what’s next?
Gottfried E. Konecny, MD: But these somatic-based tests, they’re not necessarily covered. So, we’re advocating something that may be difficult to realize in the practice. I think we have to, as a clinician, as a research clinician, start generating data that link these molecular findings to outcomes, because we have to deliver in that way. We can’t just propose we have to do these tests. We have to demonstrate that there are clinical implications, otherwise we won’t get broad coverage.
Matthew Powell, MD: And we still have a lot of people not even testing the low-hanging fruit of BRCA1 and 2.
Bradley J. Monk, MD: Yes, the germline type.
Robert L. Coleman, MD: Exactly, that’s clear.
Bradley J. Monk, MD: So, the NOVA trial was a maintenance trial within 8 weeks of response to platinum, I get it. We’re lucky that we run basically almost all of these trials—not every single one, but a lot of them. One of the trials with niraparib is called QUADRA, the idea to make it a treatment sort of opportunity. Tell us about the QUADRA trial, because again, I have the PI right here.
Katie Moore, MD: The QUADRA trial is a single-arm, open-label phase II trial of niraparib. Initially, it was really in anybody with recurrent disease, and they were, of course, collecting patients with BRCA mutations and HRD status. Over time, it morphed into only fourth- and fifth-line therapies, so it limited the number of prior lines. And now it’s only enrolling 2 HRD-high patients as we finish it out. So, the eligibility has tweaked over time, but in general, it’s a recurrent disease, single-agent confirmation trial that niraparib is an effective therapy at the time of recurrence.
Bradley J. Monk, MD: Right, because we already have olaparib and rucaparib as treatment, and we want niraparib as treatment. And the beauty of your wonderful study is that it will take all-comers: it will have some HRD in there, and it will have some BRCA. The first label of olaparib was just germline. The next was germline and somatic rucaparib. I’m hoping that with niraparib treatment, the QUADRA trial, we’ll have more than germline and somatic, maybe HRD, maybe even all-comers. We have to see the data. The beauty of NOVA, SOLO-2, and ARIEL2 is that the platinum sensitivity is, at some level, a biomarker.
Robert L. Coleman, MD: And I would say that the test to identify those patients is getting better and better.
Bradley J. Monk, MD: It’s still incomplete.
Robert L. Coleman, MD: It’s still incomplete, because we’re still seeing completely wild-type patients responding to these drugs, so we do have some room to go. I think, maybe, we ought to just briefly talk about the other trials that are actually looking at a comparison to chemotherapy.
Bradley J. Monk, MD: Because that remains a question.
Robert L. Coleman, MD: That remains a question, right? And I think most of us would probably agree that patients, when they’re on these drugs, like being away from chemotherapy.
Bradley J. Monk, MD: We need some direction. Go ahead, explain SOLO-3.
Robert L. Coleman, MD: Just briefly, these trials, ARIEL3 and SOLO-3, are really set up to try to look at this against chemotherapy, non-platinums and platinums in ARIEL4. But the idea is to have some context.
Bradley J. Monk, MD: SOLO-3 is olaparib versus 4 choices of chemotherapy, BRCA-mutated. It’s interesting, none of it is platinum.
Robert L. Coleman, MD: Right, no platinum.
Bradley J. Monk, MD: And then ARIEL4 is the same, but if it’s for more than 12 months, it puts platinum in, because that’s really a fair comparison.
Robert L. Coleman, MD: Yes, it just gives an opportunity.
Katie Moore, MD: We have the NRG-GY004 trial, so through the NCI we have a platinum-sensitive, olaparib versus chemotherapy, and a platinum-resistant, olaparib versus cediranib.
Bradley J. Monk, MD: With olaparib/cediranib. Thank you for that. We’ll sort that out.
Katie Moore, MD: I’m glad you brought that up because I think that’s the next thing we have to know, because we have a maintenance indication and we have treatment indications. And so, now we have to figure out, are you going to use PARPs again? We’ll probably talk about that. If not, what’s your best place to put them? What’s the best time to use them, maintenance or treatment?
Robert L. Coleman, MD: A sequencing piece, yes.
Katie Moore, MD: So, we have to know treatment versus what we would do otherwise, before we can compare it to the maintenance. We don’t have that information.
Robert L. Coleman, MD: The good news is that now the field is being developed so that we can actually make some of these decisions.
Bradley J. Monk, MD: Well, thanks to all of your hard work and for the wonderful patients and caregivers that allow these studies to happen.