Key Considerations for Treating Recurrent Ovarian Cancer

Transcript:

Bradley J. Monk, MD: Let’s talk about recurrent disease. That’s the fun part, right? And we have some very exciting new data to present about recurrent disease. Since the last time we did one of these panels, which was just a few months ago, we have gotten 2 new PARP inhibitors. The last time we spoke, we had one: olaparib. Now we have rucaparib and niraparib, and we’re going through that. In fact, right before our last OncLive^® panel, we’d just gotten bevacizumab approved in the platinum-sensitive relapse setting. We’ve now had time to digest that. So, essentially within the last 6 months, we’ve had 3 new approvals in targeted therapy: 2 PARP inhibitors and antiangiogenesis. It’s so exciting.

Matthew A. Powell, MD: If you want to throw pembrolizumab in there, you can.

Bradley J. Monk, MD: What are the factors that you consider, Gottfried, in making therapeutic decisions for recurrent ovarian cancer?

Gottfried E. Konecny, MD: Well, definitely having information on tailored treatments towards PARP, whether a BRCA mutation is there or not.

Bradley J. Monk, MD: A molecular signature.

Gottfried E. Konecny, MD: A molecular signature is important, I think. Again, the number of prior lines, shat types of chemotherapy were given—platinum-sensitive, platinum-resistant.

Bradley J. Monk, MD: Maybe time from last platinum?

Gottfried E. Konecny, MD: Right. And then quality-of-life issues: what does a patient expect from treatment or not? There are wonderful options available right now.

Bradley J. Monk, MD: Rob, how important is cell type in treating recurrent ovarian cancer? So, molecular signature, number of lines in therapy, platinum-free

interval, and the residual toxicities. How important is cell type?

Robert L. Coleman, MD: I think it’s becoming more and more important because of those other factors. So, for the molecular signatures, outside of BRCA versus non-BRCA, now many of us who have trials in this setting are finding agents that would be focused on those specific defects. For instance, clear-cell ovarian cancer has a frequent alteration of PI3 kinase/MET kinase pathways. And now even ARID1A, which may lead us to the EZH2 inhibitors, will turn out emergent. It may actually then get into Matt’s point: that we may have higher mutational loads that, potentially, in that situation, maybe direct us to use I-O therapies based on those features.

Bradley J. Monk, MD: So, Matt, do you treat mucinous recurrent ovarian cancer the same way you would the more typical high-grade serous disease?

Matthew A. Powell, MD: I wish we had enough data to make that decision.

Bradley J. Monk, MD: We try.

Matthew A. Powell, MD: It’s too hard in the front-line setting, and I really think that’s much more of a GI focus than has been the trend. I think Mike Fromowitz at MD Anderson has led some of that effort, but I work a lot with one of my GI oncologists, and they’re typically getting more GI regimens.

Bradley J. Monk, MD: Like HIPEC.

Matthew A. Powell, MD: Yes, and I think there may be a role for HIPEC.

Bradley J. Monk, MD: I do, too.

Robert L. Coleman, MD: But to that point, we see higher levels of HER2 alteration, copying or variances. This is an area where we’re focusing on those types of agents—or cyclin-dependent kinase aberrations. So, we see them more frequently in these particular cell types.

Bradley J. Monk, MD: How about low-grade serous disease, Katie? Do you treat low-grade serous recurrent ovarian cancer differently than high-grade serous?

Katie Moore, MD: I think we’re starting to. It’s a rare subtype of a rare tumor.

Bradley J. Monk, MD: MET kinase alterations rather than P53 signature.

Katie Moore, MD: Patients are often platinum sensitive, just because we debulk them. They got chemotherapy and then they wore out a period of time. But we don’t really feel like that has the same prognostic implications that it does with high-grade disease. So, it’s really not uncommon to have a patient with platinum-sensitive, low-grade disease that you don’t necessary retreat with platinum—or you might. But it doesn’t tend to work once it comes back. We sequence the treatment as we’ve been talking about. We look for those genomic alterations. We look hard for BRAF, which is about 8% to 12%, depending on the series. Of course, the MEK data are still emerging. We look at hormone status. We’re looking at mutations in hormone status to try and figure out what hormone or what hormone blocker to use in that population. Bevacizumab is an active drug.

Bradley J. Monk, MD: Absolutely.

Katie Moore, MD: Baseline case series, but pretty big case series, from big cancer centers, we do treat them differently. They get all the same stuff.

Bradley J. Monk, MD: But low-grade serous is definitely different.

Katie Moore, MD: It’s a different disease.

Bradley J. Monk, MD: It’s a hormone disease, maybe. It’s a MEK disease, maybe. It’s a bevacizumab disease, maybe.

Matthew A. Powell, MD: It’s a surgical disease. I think we are much more likely to reoperate on those patients. Now, the question is, am I helping them? They don’t respond. The patients do well…

Gottfried E. Konecny, MD: The medical oncologist. Everybody ends up there.

Robert L. Coleman, MD: I think because it’s in the ovary, we’re so connected to having to have to use chemotherapy. And this is a disease where even if we find equivalence to chemotherapy, I’d love to have that option because these patients don’t progress rapidly and they’re going to get a lot of exposure. They get imaged way too much. And as Katie mentioned, there’s a way to recycle and use multiple different hormonal avenues.

Gottfried E. Konecny, MD: I think you exhaust the hormonal pathway. It is the trove to dive in, where you have molecular alterations.

Robert L. Coleman, MD: Absolutely, yes.

Gottfried E. Konecny, MD: So, for all the things that are progressing in other diseases—such as CDK4/6 inhibition, hormone receptor signaling, bevacizumab—we need better and more coordinated trials for low-grade serous because they’re relatively rare. And remember, the MEK inhibitor trial had to close.

Bradley J. Monk, MD: I’ll have it next year at ASCO.

Matthew A. Powell, MD: But again, they’re very hard trials to do. They have calcification, and I think RECIST criteria is probably very suspect for following these patients, because they don’t die, they calcify.

Robert L. Coleman, MD: It’s very difficult, I agree.

Transcript Edited for Clarity