Ovarian Cancer: Evolving Concepts Around Systemic Therapy - Episode 6
Bradley J. Monk, MD: This really is the issue, Tom Krivak. You said you believe in maintenance therapy, and so do I. I think all of us do. I think that’s the evolution of our field. But now the question is, “What maintenance therapy?” I understand, cross-trial comparisons are inappropriate, but clinical decisions are appropriate and made every day. As we look at this, PAOLA-1 is provocative because of the active control. I always say if you can’t beat something, compete against nothing. Many of these PARP inhibitor trials competed against nothing. Well, this year, there was a competition against a very active—in fact, now an FDA-approved—control.
As we look at this, this is a key question. I don’t know what you’re going to say, and I understand that cross-trial comparisons are not appropriate. But when you make clinical decisions, do you look at the hazard ratios of PAOLA-1 and PRIMA—PARP alone versus PARP–bevacizumab [Avastin]—or do you look at the medians? For example, Sharyn said in the HRD [homologous recombination deficiency] non-BRCA group, which is the example patient we just talked about, the median is 28 months. Or do you say that you can’t really use that? Certainly, the elephant on the table is this sequential therapy. Maybe we need to look at bevacizumab and then PARP, or PARP and then bevacizumab, or the combination. We’ll never have that information. How do you incorporate this information that Sharyn so articulately reviewed with us?
Thomas C. Krivak, MD: That was great, the way Sharyn and Tom and Katie and everybody reviewed the data. The way I look at it is that we have options. I like testing for HRD. I know we don’t have any FDA labels, but given the fact that we have the HR [homologous recombination]–proficient group showing no benefit with dual therapy, when I see the HR-proficient group, I want to use single-agent niraparib or single-agent Avastin. In the HRD-positive group, the patients who have homologous recombination deficiency, that’s a tough question. Should you go with both? Could you look at the absolute benefit versus hazard ratios? To me, they both work. Which is going to work better? I don’t think we’ll ever get that trial. If I have a patient who had really bad thrombocytopenia and issues with her platelets, I may be a little less hesitant to put her on niraparib and favor Avastin with olaparib. I’ve heard some people say, “Just give olaparib alone. That’s where you’re going to get your maximum benefit instead of olaparib-bevacizumab.” But the trial was olaparib-bevacizumab. I would use that. If somebody had a massive PE [pulmonary embolism] and doesn’t want to be on bevacizumab, then I would use single-agent niraparib.
I struggle regarding the hazard ratio/absolute benefit. Katie had a very elegant study with SOLO-1, and it was olaparib versus nothing. When you look at the hazard ratios, I always wonder what the hazard ratio would be in PAOLA-1 if there was no active treatment. Should the BRCA-mutated patients receive olaparib with bevacizumab? That’s the struggle that I have. But across the board, for all 3 or 4 subsets—what I just talked about—I’m going to give them something based on adverse effects and based on their molecular marker. Or at least offer them something and they can make that decision. But that’s how I look at how these 3 studies give us options that are all complementary. Really, when you look at all 4 studies, they solidify that we need to be using maintenance therapy for these patients.
Bradley J. Monk, MD: That’s the key point. Remember, Tom Herzog, you talked about PRIMA very nicely, but it was a very high-risk population. It was the population that we feel the most comfortable using bevacizumab in. There was a paper at the SGO [Society of Gynecologic Oncology] meeting that went through some of the subpopulations of PAOLA. Do you have that on your mind?
Thomas J. Herzog, MD: It didn’t really teach us a whole lot in terms of what we already knew, but it certainly reinforced our understandings. I could throw it out to the panel, for those of you who may not have read it. Who do you think did best? They looked at whether you had primary cytoreduction versus interval cytoreduction and if you had residual disease or didn’t have residual disease. Then they looked at what those hazard ratios were within the PAOLA subgroups. What they found was that if you had the primary cytoreduction, your hazard ratio was 0.52 versus 0.66. But with no residual disease, you got it all the way down to 0.47, and that was a big difference compared with 0.61. It’s a pretty big difference there, approximately 14%. With residual disease, there wasn’t a difference. It was really no residual disease and primary cytoreduction: those patients did quite a bit better. But the treatment effect, other than with residual disease, was across all subgroups.
Bradley J. Monk, MD: Thank you for that. And again thank you, Katie Moore, for leading the meeting and for getting these out in the public domain.
Transcript edited for clarity.