Future Directions for Treating Advanced Ovarian Cancers

Transcript:Bradley J. Monk, MD: I’m going to give you guys an opportunity for a closing remark. I’ll let you go first, Angeles. What’s your observation that is changing the most rapidly in the ovarian cancer treatment space?

Angeles Alvarez Secord, MD: Well, it’s the access to these novel therapies. We went how many years without any FDA approvals. I think the last one, was it 2006 with gemcitabine with carboplatin?

Bradley J. Monk, MD: Yes.

Angeles Alvarez Secord, MD: Those were 2 chemotherapy drugs that we got approval, but I think most people were utilizing them anyway. And then, to get access to these drugs, I do think it has made a difference for our patients. We were given some additional tool in our toolbox to use to treat women with ovarian cancer. And we’ve seen, over time, incremental gains in overall survival for women with ovarian cancer.

Bradley J. Monk, MD: And it’s exciting because we just, on December 6th, got bevacizumab, platinum-sensitive. February 23rd is the PDUFA date for rucaparib. We have SOLO-2 coming for olaparib, and then NOVA for niraparib. It’s hard to keep track of it. So, Katie, what do you think is your most exciting thing as this field rapidly evolves?

Kathleen N. Moore, MD: There are so many exciting things, but I think the thing I’m interested in figuring out—and Rob and I are going to have a spirited discussion about this—is we have the NOVA data, so we’re all excited to use niraparib in maintenance and SOLO-2. And then we have very compelling data that the drug is effective as a single agent for treatment. So, I think one of the big questions right now is the sequence question that you alluded to. In the past, who cared if you had doxorubicin before gemcitabine before Taxol. You’re going to use them all, right? Now, maybe it doesn’t matter, but we need to figure out if treating small-volume disease in maintenance makes more sense or do you set people up for these reversion mutations and BRCA and make them less likely to respond to maybe PARP inhibitors later or even other chemotherapies later? And you should reserve PARP inhibitors for larger volume recurrences. If you treat larger volume, are you more likely to get a reversion mutation there? I don’t think I know that information yet, so what’s the most effective place to use them and the safest? I think they cross a little bit, and I don’t know that we understand that yet.

Bradley J. Monk, MD: So, sequencing?

Kathleen N. Moore, MD: Sequence is important or may be important.

Bradley J. Monk, MD: Is it about drug resistance? We haven’t really talked about drug resistance. Is that really what we need to work on? Because, tumors, in the end, become resistant to all of these agents.

Robert L. Coleman, MD: Correct. Yes, I think resistance and augmentation are the 2 big areas going forward. I think you asked Angeles what she’s really excited about, and I think that one of the reasons we’re having this discussion is because the industry is engaged in this process. The FDA has decided to work with us in looking at alternative endpoints that can lead to these regulatory approvals. That has brought an influx of desire to match with the explosion of science—so, talking about which are the best combinations, talking about what do we do in resistance, how to measure that in real time. Like, if you can know what was going on in every cycle as a response to your intervention and you could alter therapy, maybe we would have these mini PFS gains on all these different regimens and we’d use in sequence because it was informed by something we did along the way. So, to me, that’s what’s exciting. I’m super excited about all of these specific areas because they’re linked to science that makes a lot of sense and we can interrogate, and we have interested partners because we have a light at the end of the tunnel. That is very exciting to me.

Bradley J. Monk, MD: I’m interested in biomarkers. That’s what I’m excited about. I’ve worked on bevacizumab for a long time and it was always in unselected patients, and quite frankly, it really didn’t work that well. I’m interested in the fact that the HRD biomarker, which predicts PARP inhibition, also shows neoantigens and maybe increase in mutational burden. And there might be, I don’t mean to overstate it, a cure for some patients in that common biomarker for a combination of IO and PARP inhibitors. But that’s what I’m interested in. So, Tom, I want to thank you publicly for your leading the FDA consensus conference, for spearheading SGO, papers on regulatory approval. And out of respect, I want to give you the final word.

Thomas Herzog, MD: You were going to ask what’s exciting. I think one of the things that’s really exciting is taking everything that you all said, and Rob, you said it well in terms of the “explosion of science.” We also have an explosion of our ability to manage “Big Data” and to look at that. And we’ve had a real change, a paradigm shift. I know that phrase is overused, but it really has occurred in terms of how we conduct clinical trials and how they’re going to look in the future. So, we’re looking for bigger deltas, bigger changes. We can do that with less of our most valuable resource, and that’s our patients. It’s exciting because we have so many possibilities now. All those combinations are multifactorial, so how do we put these PARPs together? How do we put these immunotherapeutics together, and how do we put antiangiogenesis together? We’re going to have to leverage that to the best benefit of our patients. I think we’re coming to the point where our clinical trial design mechanism will be able to live up to that daunting challenge.

Bradley J. Monk, MD: Thank you for that, Tom. And Katie, Angeles, and Rob, and for you, the audience, I want to thank you for tuning in. So long for now.

Transcript Edited for Clarity