Ovarian Cancer: Evolving Concepts Around Systemic Therapy - Episode 4
Bradley J. Monk, MD: Let’s just assume, Katie, that you saw a patient who comes into your office and says, “I responded to my frontline chemotherapy. I had a serious advanced ovarian cancer, and my doctor did this HRD [homologous recombination deficiency] test; here it is.” And she says, “My doctor is not very passionate about recommending that I get PARP maintenance, and I don’t have a BRCA mutation; it’s an HRD test.”
Would you say—with the same passion you had for SOLO-1—to this patient that this is a no-brainer. You need PARP maintenance, you have a molecular marker, as Tom alluded to. This would be more than a doubling of the median progression-free survival. The median for an HRD-positive patient, excluding BRCA, has a hazard ratio of 0.5—Tom, what you said—going from 8.2 to 19.6 months. It is more than doubling of the progression-free survival. What would you tell that patient, Katie? I’m going to ask you, Tom Krivak and Sharyn Lewin, the same question.
Kathleen N. Moore, MD: You asked me about my passion. I do believe that PARP inhibitors are the standard of care with shared decision-making for patients who have BRCA-associated cancers. For patients without BRCA-associated cancers, they are a standard of care, but there’s a spectrum in there. This would be on the stronger edge of evidence. The HRD group was 1 of the analytical subgroups of PRIMA, and it met its end point. I believe that, and we’ll get into the debate later. I would strongly counsel this patient regarding the potential benefit of use of niraparib, and then the known risks and benefits. I would especially talk about what the gains would be in terms of progression-free survival and what that means, without an overall survival end point that we won’t have for quite a while; though in PRIMA, we may get it much earlier than on some of the other studies. Then it would be shared decision-making between the patient and me.
I think this is a little different in that there are options for both. Some patients just want to do surveillance. I don’t know if I’d beg someone to start maintenance, which I do with BRCA-associated cancers. But I would strongly recommend this. I think it makes a lot of sense. We know these patients are going to recur. We just have to stop talking about all these cured high-stage patients. They don’t exist. I really wish they did, but they don’t. Try to prolong response as long as possible. I just don’t know why you wouldn’t.
Bradley J. Monk, MD:I like this idea of shared decision making. But let’s face it, when you give the patient the option of taking a pill that might have some adverse effects versus going on vacation—trust me, you can go on vacation and take a PARP inhibitor too—they have a tendency to take the easy way out. It’s just human nature, right? Every patient thinks they’re cured. You say they don’t exist. Every patient thinks they’re the exception, and I don’t know why the doctor thinks they’re the exception, but there are many care providers who do.
Kathleen N. Moore, MD: If you present observation as an equivalent option—and it’s listed like that in the NCCN [National Comprehensive Cancer Network] Guidelines, which is mind-boggling—then they’ll think, “Oh, I could do something or not do something? I’m going to not do something.” We invoke the counseling.
Bradley J. Monk, MD: That’s what I’m trying to discuss here. It’s the strength of the recommendation in everything we do. Whether it’s a Gardasil 9 vaccine or PARP maintenance, it’s the strength of the recommendation. Sharyn, how strong would you recommend this? HRD in hand, a patient who didn’t receive bevacizumab and responded to frontline therapy comes to you and says, “Dr Lewin, you have a great reputation. Do I need maintenance niraparib?”
Sharyn N. Lewin, MD: Honestly, I agree with everything that Katie said. I want to take a minute to highlight the importance of frontline germline testing, which unfortunately not 100% of women with ovarian cancer receive. There were data at the SGO [Society of Gynecologic Oncology] Annual Meeting showing about 60% do. I don’t know why it’s not quite 100%. But I agree, it really is shared decision-making. I am a big biomarker believer. I know the inherent problems with the subgroup analyses. But I think if the patient does have HRD—and of course if she has a BRCA somatic or germline mutation—I’m going to strongly encourage PARP maintenance.
Bradley J. Monk, MD: Tom Krivak, how strong is the recommendation? HRD in hand.
Thomas C. Krivak, MD: We talk about financial conflicts. What I can say is that I have a biomarker conflict too, in that I believe in HRD and I believe in maintenance. When I give talks, I automatically say that I graduated fellowship in 2002. I thought Maurie Markman’s trial of 12 monthly cycles versus 3 maintenance paclitaxel was great, and I’ve used maintenance therapy ever since. It’s important because what’s really moved the needle has not been the up-front 6 cycles of whatever therapy we give: the maintenance therapy has moved the needle. To me, if somebody has an HRD-positive tumor, I would strongly recommend maintenance, whether it’s single-agent niraparib or a combination therapy. But I would have to say part of my bias is that when I see folks with advanced-stage ovarian cancer, I’m going to recommend some form of maintenance therapy, and I don’t believe in active surveillance in that group.
Bradley J. Monk, MD: People want to know what your conflict of interest is. Trust me, your conflict of interest is not because someone paid you to go to work, whether it be a drug company or your hospital. Your conflict of interest is that you have seen patients benefit and stay alive and live better with maintenance therapy. I get that. In my mind, it’s evidence and evidence based. For the audience, I’ve got 4 panelists here and myself to offer—with a strong recommendation—a maintenance PARP inhibitor in BRCA-mutated disease. With an HRD molecular signature, you can maybe soften it a little. Your head doesn’t have to explode, to quote Katie Moore, but my head would explode if someone says, “Well, I don’t know.”
Transcript edited for clarity.