SGO Highlights: Advances in the Treatment of Gynecologic Cancer

What does the latest data mean for real-world gyn oncology care? In this episode of Podium Perspectives, Robert L. Coleman, MD, FACOG, FACS and Kathleen N. Moore, MD, MS break down the most practice-relevant findings from this year's SGO Annual Meeting on Women's Cancer. Across ovarian, endometrial, and cervical cancers, they unpack how emerging data may reshape patient selection, treatment sequencing, and standards of care.

Built for busy clinicians, this focused conversation turns congress highlights into practical takeaways—bridging evidence from podium to practice. Listen now to stay current on advances shaping the treatment of gynecologic cancers—powered by Vaniam Group.

This podcast is for informational purposes only and does not constitute medical advice. The views expressed by the hosts and guests are their own and do not necessarily represent those of their respective institutions or employers.

Transcript

SPEAKER_01 0:02

Welcome to Podium Perspectives, powered by Vanium Group.

SPEAKER_02 0:11

Welcome everyone to Podium Perspectives, Advances in the Treatment of Gondabonic Cancers. This Shield highlights a podcast that shares up-to-date insights across oncology and rare diseases. I'm Rob Coleman. I'm the chief medical officer at VM Group, but also a geo oncologist at Tech Oncology. And I'm excited to uh be part of this podcast series along with my good friend Dr. Kathleen Moore, who is now at the University of Nebraska Medical Center in Omaha, Nebraska. Katie?

unknown 0:42

Hi there.

SPEAKER_00 0:42

Happy to be here. Lots of exciting data. What we saw last week at Society of Gynook. So excited to break some of it down with you.

SPEAKER_02 0:51

Excellent. Thank you so much. So let's uh let's dive in. We um we had uh kind of a nice uh late breaking session that started off the conference I thought was pretty strong. Uh and uh one of the first uh updates that we saw was the uh kind of final overall survival data from the Rosella trial, which of course was looking at uh weekly NAPPAC a taxol versus weekly NAPPAC a taxil plus a uh glucocorcoid uh receptor antagonist uh called uh relicoral. And uh we have we've seen various iterations of this over time, one of one of which was an early report demonstrated in BFS and and what looked like a pretty uh light uh impressive overall survival signal, although it was an interim analysis. And so we we we were highly anticipating the overall data, overall survival data to come out and be and proved itself to be positive. And of course, we know we found out by uh you know, like what we see oftentimes by press release that um there was a significant difference in overall survival that was um that was found in the trial, and that was obviously very important. But today, and we saw the publication, simultaneous publication today, or at the meeting with the um uh with with the final uh data. So I guess maybe maybe tell us a little about um you know what why this is important in the ovarian cancer community.

SPEAKER_00 2:13

Sure. Uh and so agree. Um glad we're starting with this one because this was, I think, one of the highlights of the meeting for sure. Uh in general, let's just I think let's just start by putting this in context to uh the history and the treatment of patients whose tumors are designated as resistant to platinum. Our one success was the Aurelia trial, which was chemotherapy with Bebacism app published in like 2014 or 15 and approved by the FDA and the um uh European authorities based on progression-free survival plus supporting patient reported outcomes, mainly around abdominal symptom improvement, but not OS, which will forever shock me that there wasn't an OS given the degree of PFS advantage. But but that was our only success for a decade and not for lack of time, just a myriad of uh well-designed studies that didn't work. And then starting in 2024 with Mirasol, and then um now we're here with Rosella, we've had three clinical trials with I would say modest uh improvements in both progression free and overall survival, uh, which puts us in a very different space for patients um than we were two years ago. We now have several what we expect to be effective regis uh for patients with resistant tumors, where prior to this we really hadn't picked one. Um and it gives us the opportunities really individualize for patients, uh, think about sequencing uh in a in a rational way, in a science-driven way, uh especially with the additional drugs that are coming after this, and we'll talk about those. Uh, and and I think provides our patients with some rays of hope, you know, that we are gonna push out how long they can live with these therapies. So just in general, this is important for that reason. Like we have not had enough wins for our patients in this space, and we just are really on fire right now with um with medications that are pushing things forward. So that's my first statement. My second statement would be this is a nice uh approval because PFS OS, the OS advantage um is kind of in the same range as Mirosol. You know, we're talking now about uh 35%. Mirosol was a 33% reduction in the rate of death uh for patients randomized to napaclitaxil relequent as compared to nappax lataxol alone. Um and it's also worth noting that napaclataxol performed in my might equivalently to weekly paclataxil. So it wasn't an underperforming control arm here, it really did just work. Um and you know, I think that's quite important and not biomarker gated. So while we continue to try and develop things so we can really individualize for patients with biomarkers, some tumors don't have biomarkers, uh or maybe not as many as we would like. And this gives us an all-comer opportunity with the expectation of benefit. So, you know, I think this was really noteworthy for those two main reasons.

SPEAKER_02 5:23

Sure, sure, yeah. And and of course, this uh, you know, uh you and I both have seen the uh kind of landscape evolve with the recognition of how important weak taxanes have been for the backbones of these of these um uh regimens. But in this particular trial, we use napaclataxol. And what was the why was that why was that of interest, at least with this particular drug?

SPEAKER_00 5:45

Yeah, so relicorlin is a glucocorticoid receptor antagonist. Uh and the science is kind of beyond the the scope of this podcast, but uh you're and my good friend Dr. Neil Soods have been you know working on this for, I don't know, well over a decade.

SPEAKER_02 6:01

Yeah, 15 years, yeah.

SPEAKER_00 6:04

We've been hearing about this, the the preclinical work and the hope of targeting glucocorticoid receptors, which uh are overexpressed on a number of tumors, but particularly on ovarian cancer and even with physiologic doses of steroids, when you have that overexpression, and certainly in sort of stress settings like cancer, where there's an abundance of circulating um steroids, and you have these excess receptors, it ubreculates anti-apoptotic pathways that in and of themselves help tumors be resistant to a lot of um chemotherapies, but preclinically the combination with taxanes look the strongest for potential um additivity. Uh and so we've been hearing about the promise of this for a long time, but it's just a really hard receptor to drug. Uh and so relichorate is really the first effective and tolerable, tolerable being a key point um glucocoid receptor antagonist. And so keeping that in mind, if I'm trying to antagonize an abundance of glucocorticoid receptors, I don't want excess ligand circulating in the way of exogenous steroids. So when we use weakly paclitaxel, we probably use too much steroids, let's just acknowledge, but we do pre-medicate with um pretty high doses of steroids. And so there is the theoretical risk that you could confound the efficacy of this medication, you know, with that on board. So with NAT Paclitaxol, you don't need to use the pre-medications because there's not um cremophore, which is what really drives our use of of the steroids. And so that um you know that helps us um use a taxane without confounding the efficacy with a steroid, and probably just better in general. Honestly, we use so much steroids on our patients, it's probably just better for the work too. Yeah.

SPEAKER_02 8:02

Yeah, yeah. We even got in the weekly uh format, we even got used to you know reducing those steroids because it's it's every you know it's every week they would get they would get a lot of steroids with it. So yeah, I think I agree with you. I think this is um this is an important um uh milestone for us to hit third third you know, third trial with a with an OS benefit in a very difficult to treat space. So that's great. We'll see as uh as this uh continues to evolve. Obviously, there's some new uh combinations that are coming with that regimen, and uh we'll see how how it goes forward. Let's uh switch gears a little bit. Um also in that session, we saw uh a uh report on a very highly anticipated trial. You and I have been watching for this for a long time on GY019, which was actually looking at an endocrine strategy for low-grade serous. And and maybe we'll first of all ask you is you know, how low-grade serous and high grade serous, they have they both have a lot of the same terms, but obviously they're very different diseases. And um maybe we can start um uh talk a little bit about uh just the biology differences uh, but in this trial, you know, we had continuously seen uh endocrine therapy being used in the recurrent setting, and this was a frontline trial that was set up to address uh a kind of a standard approach, which in and of itself hasn't actually been proven. It was it was obviously uh chosen by the totality of data looking at chemo followed by endocrine maintenance. That was never actually uh uh formally assessed in a frontline in a uh phase three setting, but it was felt to be a good standard to follow. Um, and then that up against a pure endocrine, which was left was all alone, uh, based both uh given tilt progression. And um, and this was a you know a trial that was set up to address whether or not the new endocrine therapy was non-inferior. And so a lot of stuff to unpack in this particular concept design, but maybe we just start with a brief kind of reminder of why low-grade and high grade Cirrus are different diseases, even though they have a lot of the same terminologies.

SPEAKER_00 9:59

Yeah. So it's really uh Rachel Grisham uh also presented at SGO. I don't know if we're gonna be able to talk about um RAMP 201, but there was a lot of, I think there's just a lot of growing excitement around low-grade Cirrus. Finally, uh patients that suffer with this disease finally having medications advanced for them in particular, not as just an add-on, you know, to to to things in the past. So low-grade cirrus should have a different name from high-grade cirrus because I think it just seems like a different name. It's not, it's you know, high grid serous is you has ubiquitous loss of TP53. We do not see that in low-grade serous. In fact, if you have a low-grade serous that has a TP53 mutation, could be a mixed, I guess, but it's not low-grade cirrus. Um, those are very different, like the the high grade serous is a fallopian tube cancer. Low-grade serous really can start um in a variety of places, um, but it's starting in the ovary or sometimes the peritoneum. Uh, they are largely driven oncogenically by changes in the map kinase pathway. So K-RESP being our most common uh mutation, but you can see NRESP, BRAF. You find ubiquitous uh estrogen receptor positivity. Uh we don't even have to test for it really uh anymore. And those are very different from high-grade serous, where KRAS mutations are incredibly uncommon. Not never. You will you'll find amplifications in high-grade cirrus because it's a copy number-driven um cancer, but mutations are really uncommon um for KRAS and high-grade cirrus. You'll find estrogen receptors all the time, but they mean nothing. Like they're not driving anything, they're just there for the ride. And in low grade, they're targetable. So these are really different tumors and the expectation of response to cytotoxic chemotherapies and endocrine therapies are opposite in each of these cancers from one another. Uh, and so really understanding that and starting to design studies and sequencing of studies for patients who have advanced repair low grade serous is really critical.

SPEAKER_02 12:12

Yeah, and that's great. It's a really nice context to put the frameworks for this trial. And we obviously we've evaluated several different types of drugs over the time period. It's a it's a you know we would classify as a as a rare disease. Um, and that's one of the reasons I like the idea of like renaming it something else so that it gets out of that confusion. But um this particular trial was done in a in a uh in a is a non-inferior design. These are somewhat complicated uh just in general to understand how to interpret. They're also complicated on how to actually design. And what we did in this trial um is the we, you know, we set up a margin that we were comfortable uh allowing to show uh a um you know a what what the hazard ratio that we would accept. Um and in this particular trial, because of the concern that maybe we would be putting patients at risk, we had built in uh these interim evaluations. And what we saw at this meeting from Amanda Nichols-Fader was a report on the second interim analysis. And and maybe you could just maybe briefly tell us what they found um as the outcome in this trial for progression-free survival.

SPEAKER_00 13:21

Yeah, so what they found was number one, both groups you know really did relatively well. Um so that's kind of one thing to say. Um, but what they what the kind of analysis to uh suggested is that the use of letrozol alone as compared to chemotherapy followed by letrozol did not appear to be inferior. So not inferior, not non-inferior.

SPEAKER_02 13:54

Not non-inferior, right?

SPEAKER_00 13:56

Not non-inferior. So we can't say it is inferior, but we could not statistically rule out the probability that it's not non-inferior. And so it kind of crossed that boundary of futility that we talked about, and um, based on the statistical rules of the study, they made the decision, you know, to release the results um and sort of call this futile.

SPEAKER_02 14:25

Right. Yeah, I think that's a good way to say it. I it these are the they're incredibly hard to to um to interpret because so often these non-inferiority trials are which tend to have to be pretty big to make dissimitive statements, and many of them end up in that gray zone where they're kind where the point estimate is either above or below one, but the confidence interval is broad enough to separate across all the different distinguishing characteristics. So what we said is that you know the out the uh the the intent here was to show that these that the new regimen was not inferior to standard of care, and we couldn't we drag that null hypothesis because it was it um it was above that into the zone that was above the uh the threshold for the non-inferior boundary. So um, you know, I think I think the way that Amanda um stated during her um her uh presentation is that she said this was practice defining. So what what does that mean? I thought that was kind of a cool way to say it.

SPEAKER_00 15:25

Well, I think that it um it was an important thing to say because we're right or wrong, like I'm not here to throw stones, but the NCCN had listed letrozole as an alternative, you know, in the frontline setting. And there were many, there are many in the community who rely on the NCCN to sort of provide guidance on how to take care of um our patients in the in the best way possible. We want to give NCCN level care at least. And this is no longer, in my opinion, NCCN level appropriate care, and we should stop doing it. Um, could there be issues with the trial design? And the, you know, we included patients with residual disease. Is this we've done it all and completely resected? Might it have been different? There's lots of every time we do a trial, we're like, you know, shoulda, woulda, coulda. I wish I had done it this way, but you design the studies the way you design them, and you have to state the statistical endpoint. So practice definition right now is right now the standard of care is starting with Pacotax on carboplatin. Um, and then as you said, I mean, I guess we say that it's lectural maintenance, although it was never proven um in a phase three setting to be um superior. You know, we have data for Pacotaxal carboplatin bevismap in this in this setting as well that looks kind of good. But uh, I guess I would say practice defining in that we cannot drop the chemo.

SPEAKER_02 16:54

Right. I think that's really good. Yeah, I'll just give a little anecdote. I know we had tumor board and there's a low-grade patient uh on the uh on the uh uh uh who was on the schedule. And uh it um she um they were what she was really wanting the hormones in. So we at the end of the uh at the end of the uh tumor board we're like, listen, we're gonna have to wait until we see the results of this trial so we can make a decision as to whether she should go out of a chemo. But as it turned out, then we did see this then. So that's what that's what our recommendation will be as the chemo therapy followed by uh electrozolysis standard. That's cool. So let's um let's um just uh maybe maybe walk into maybe some of the novel therapies that we saw presented at at uh at SGO. Um, you know, these this meeting usually fills up as many meetings to fill up as as more as we learn more about the uh therapies that we want to hopefully replace our uh in all of our diseases, so inometrial uh cervix and ovarian cancer. We want we want to see the uh progress of uh new new therapies coming in that might be able to be good candidates for phase three investigation. And we had some interesting updates. Uh maybe just briefly talk about uh that uh uh very interesting drug that targets the P53 mutation, which is uh obviously an uncommon, a rare uh potential um finding for our uh for our patients, but it actually is a very selective mutation and basically an undruggable target. So what did you think about that, the the results out of the pinnacle trial?

SPEAKER_00 18:22

The pinnacle trial. Yeah, so this is uh uh I'm so so the phase one was just published in the New England Journal of Medicine uh like this month, or maybe just late March. Uh so I would encourage our listeners to to look at that. Um but Dr. Allison Schram uh who's who along with um Dr. Uh Katerina Dembrava have really led uh this trial development of risatopops. Um in TP53Y22C mutated solid tumors, the signal from the phase one in ovary was quite strong. And so this is sort of the expanded cohort of um patients with ovarian cancer with this uh rare TP53 uh hot spot mutation, which is present in about almost 4% of high grade ovarian cancer. So it's you know, we say this now, we want you to look at all of the whatever NGS you're sending. Go back and make sure you look and you know whether or not you know what the TP53 mutation is. And if it's Y22OC, uh, we want that kind of called out because this drug, I think, is is coming in coming in pretty hot. It's an oral medication. Uh there were multiple cohorts that we'll looked at. We looked at the ovari cancer cohort um here at um at the Society of Gynecologic Oncology. There were um 63 patients. So it was a pretty good number, you know, cohort, still small numbers, but for rare tumor, that's a pretty nice um numbers of patients. And you know, I'm looking right now at the waterfall plot. I know that you can't see it, but when I'm looking at this, there were only one, two, three, four, five, six, seven of them who had tumor growth. You know, and then everybody else had some gradation of tumor reduction, you know, until you hit kind of the resist response rate, which was about uh 44%. And that held irrespective of prior therapy, which is something we're thinking about a lot now. Had they had prior bibacysism ab, the response rate there was 44%. Had they had prior PARP inhibitor, that's 38 patients, the response rate's 52%. FR alpha didn't really seem to impact the activity of this medication either. So pretty consistent efficacy across a number of prior exposures. Um, and then median duration of response, which is a surrogate for PFS, is sitting right now about eight months. So um so small numbers, this is always going to be small numbers because this is a rare tumor, but we have an oral medication um with a pretty high likelihood of causing some tumor shrinkage for a clinically relevant amount of time. And with a side effect profile, and this is where I think using some of our new tools, we talk a lot, Rob, about PRO CTCAE, because I'm just gonna say it looks pretty good from a from a what we look at standpoint where the treatment emergent adverse events were very low grade, kind of nausea, fatigue, um that are there and important, but but low grade, only a five percent discontinuation rate because of adverse events makes me think that patients on this medication were were tolerating it, you know, pretty well. But we need more you know proof of that to before we say you know, patients feel great on it. But but I think this is really one of these things that it's a needle in the haystack, it's kind of like Ntrek. If you find the Ntrek, you're gonna use Larotrectative. If I find TPT3, I want to use hope and be able to use data pop. So where I use it, how I use it. I think is what the next iteration of trials will be.

SPEAKER_02 22:04

Yeah. Yeah. Is nice to follow up on the theme of kind of individualization of therapy, which we're doing across obviously also the ADCs, which we we saw some updates. And I certainly encourage people to uh to check out the data as it emerges uh in the public domain from the uh from the SGO uh conference. So why don't we uh wrap this up, uh uh Katie? It was wonderful to have you um uh on on uh I would love to do more of this. There's so much more to talk about when I said these spot so fast, but so many cool things that we could do uh as part of this uh process. And I really want to uh thanks for listening for the uh podium in this podium perspectives. And I would say make sure you stay tuned for some for as uh more and more data come become available. Uh this uh I just want to say one disclaimer that this is an uh episode is for educational purposes only and is not medical advice. But but having said that, wasn't that fun? Thanks so much, Katie. It's so great to be with you. You bet. It's great to see you. Thank you.

unknown 23:07

Thank you.

SPEAKER_01 23:11

Thanks for joining Podium Perspectives, powered by Vanium Group. This episode is for educational purposes only and is not medical advice.