Improvements in Advanced Ovarian Cancer



Bradley J. Monk, MD, FACS, FACOG: We’ve talked about these 4 categories of targeted therapy—angiogenic, PARP, I-O, and antibody-drug conjugate. I want to ask each of you what combination you’re most excited about. I get it; we said that we may be able to give them all together in the frontline setting and can cure more patients. But if you had to pick, Katie, a combination—you’ve got 4 classes now—a doublet targeted therapy, what are you most excited about?

Kathleen Moore, MD: Based on experience, I’m most excited about mirvetuximab and bevacizumab.

Bradley J. Monk, MD, FACS, FACOG: Yes. We really haven’t talked about that, but that is an exciting opportunity and we’ve seen some dramatic and durable responses. Thank you. Tom, what doublet targeted therapy are you most excited about? You talked about a number of them.

Thomas Herzog, MD: I think the safe bet is a PARP inhibitor and an antiangiogenic therapy. I think the one that is more likely to fail is PARP and I-O.

Bradley J. Monk, MD, FACS, FACOG: Leslie, what doublet targeted therapy are you most excited about?

Leslie M. Randall, MD, MAS: Oh, the failure—PARP with I-O. I’m looking for duration of response, not response rate.

Bradley J. Monk, MD, FACS, FACOG: Isn’t that great? I asked 3 of you the same question, but I got different answers, right? I heard antibody-drug conjugate/bevacizumab, bevacizumab/PARP, I-O/PARP. Oliver?

Oliver Dorigo, MD, PhD: I will say something different. I think there is evidence or a belief that bevacizumab and an immune checkpoint inhibitor might have synergy. Bevacizumab has been shown in preclinical models to increase infiltration of T cells. VEGF actually builds a shield around the tumor. It doesn’t let the T cells in. You can make a tumor hot with bevacizumab. In these cases, I think an immune checkpoint inhibitor that activates T cells in the tumor might be more effective.

Bradley J. Monk, MD, FACS, FACOG: That’s stimulating to me, right? We have multiple, active targeted therapies, multiple combinations, that we share different levels of excitement for. But the key is clinical trials, right? I want to thank all 4 of you for your commitment to clinical trials. This has been extremely informative. Before we end this discussion, I’d like to hear final thoughts from each of our 4 panelists. Oliver, you have the first final word.

Oliver Dorigo, MD, PhD: Well, thank you for moderating this very exciting discussion. I really appreciate it. We’re in an era of rapid drug development. I think we are finally moving the dial in ovarian cancer. I tell my patients, almost on a daily basis, that we have made progress. I’m personally very excited about the next steps.

Bradley J. Monk, MD, FACS, FACOG: Leslie, do you have any final words?

Leslie M. Randall, MD, MAS: Yes. I couldn’t agree more. I’d just add that we actually have a prevention method now, and that’s with identifying our BRCA mutation carriers and operating on them.

Bradley J. Monk, MD, FACS, FACOG: Tom?

Thomas Herzog, MD: Thank you for your wonderful moderating today. Oliver, earlier you said it well—the translational components of all of these trials. I think the first message is, these patients have to be going on clinical trials or we’re not going to be able to solve all of these difficult issues. All of these different drugs are coming through the pipeline. We have to have more patients on trial, and we have to do these translational components to understand how to make the next generation of trials more specific for these patients.

Bradley J. Monk, MD, FACS, FACOG: Katie?

Kathleen Moore, MD: I don’t know what I could add to that. I agree. Just looking at it a bit differently, as a clinical trialist, so many great drugs have been designed for ovarian cancer from the beginning. These are not just the leftovers that didn’t work in breast cancer or other diseases. Smart, well-designed clinical trials are coming out at a rapid pace. I do all early-phase drug development. Patients come in and they’ve been told that there’s nothing else for them. At our site, we can say that we have a lineup of things for them. We can really provide patients with exceptional agents that help prolong their lives and contribute to science. I think patients are really excited about the fact that we care enough about them that we’re working with hard-to-develop drugs.

Bradley J. Monk, MD, FACS, FACOG: I’d like to add that there’s value in high-volume centers. Fortunately, gynecologic cancers are rare. In a low-volume setting, there might be some differences in opinion. But experience is important here, and I think that is important for patients.

Thomas Herzog, MD: And awareness of clinical trials and awareness of how to manage toxicities.

Bradley J. Monk, MD, FACS, FACOG: Thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us. We hope you found this Peer Exchange® discussion to be useful and informative.

Transcript Edited for Clarity.

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