WEBVTT
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Could cure for cancer be closer than you think?
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Welcome to Life from Stage 4, where MBC takes center stage as we talk to experts, share inspiring stories, break down signs, and shine the spotlight on what matters most.
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Because when it comes down to it, the spot, for us and by us, is all about us.
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Welcome back to Life from Stage 4.
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I'm Victoria Goldberg.
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In the last month, if you've been following along, you know we spent a lot of time, and rightfully so.
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Deep in the weeds of Serena 6 and Cam Zastri.
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Between our patient panel episode, our conversation with Dr.
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Sarah Sammons and Dr.
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Neil Vassan, and everything in between.
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We have really given the story the attention it deserved.
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And it deserved it.
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Using a block test to detect resistance before a scan even shows progression is a genuine paradigm shift, even if the regulatory path is still being sorted out.
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But to understand why all of this matters, it helps to zoom out.
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Dr.
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Erica Hamilton, in her recent interview with Oncology Brothers, put it well.
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For over a decade, our advances in ER-positive HER2-negative breast cancer have come from targeted agents.
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CDK46 inhibitors, PI3, PI3K and AKT inhibitors, but we haven't had a truly novel endocrine backbone since Volvestra.
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This is what has changed.
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We are now in the era of oral CERDs, and the field is moving fast.
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In the past year alone, the docastron, a first in-class product degradator, a different mechanism of action from a CERD, one that flags the estrogen receptor for destruction and recycles itself.
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To do it again, received FDA approval for ESR1 mutated metastatic breast cancer based on the Very TAC2 trial.
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Immunestrin.
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Another oral CERP received FDA approval as a single agent and updated amber 3 data from SCO2026 showed it improved overall survival in ESR1 mutated patients to 35.4 months versus 23.1 months with standard therapy.
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And when combined with IBRANDS, progression-free survival nearly doubled.
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The field is now seriously asking whether CERT targeted agent combination should become the new standard of care for most PSR1 mutated patients.
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And that is exactly the question.
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There are now multiple oral CERDs, pro-TAC, new CERMS, new serums, combinations being explored across lines of therapy, trials in the first-line setting, adjuvant trials.
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The landscape has become rich and frankly very complex.
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We have spent our last few episodes focused on Serena 6 and Kamisestrin.
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Today it is time to talk about everything else.
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Joining me, my co-host and friend Abigail Johnston and Dr.
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Sarah Pramji, a medical oncologist from Sarah Canon in Nashville.
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And so, without further ado, let's get started.
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Abigail Johnston is with me.
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I so love having her with us.
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And now we have a new friend that we just met.
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Her name is Dr.
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Sarah Premji.
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And we're here to talk about the fast and furious development in the space of metastatic breast cancer for HR-positive HER2 negative population.
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And Sarah, please introduce yourself and tell us about yourself.
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Absolutely.
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Thanks so much for having me.
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So, just as Victoria mentioned, my name is Sarah Premje.
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I serve as the assistant director of breast cancer research at Sarah Canon in Nashville, Tennessee.
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I graduated from Mayo Clinic in Rochester, Minnesota, where I discovered my love of breast cancer and got a chance to work on some really cool projects over there that I'm continuing on here, along with my role in serving as the principal investigator on several different trials, looking at early phase development of novel therapeutics in breast cancer and also in the phase three space.
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So happy to be here, happy to provide any insights, and thanks again for having me.
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Absolutely.
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We honored to have you with us.
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And Dr.
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Erica Hamilton has introduced us, and we love Dr.
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Erica Hamilton.
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So thank you for being here.
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She is a wonderful mentor.
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I'm so lucky to learn and get to work with her.
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Yes, yes, we feel the same way.
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So let's start.
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It will be important for us to start from the beginning and actually talk a little bit about the landscape and what is currently happening with this space.
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Yeah, absolutely.
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So I feel like hormone-positive breast cancer, it's evolved rapidly and really over the past decade or so has revolutionized.
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So we do know that in early 2015, I think it was February of 2015, palbocyclib, our first CDK4-6 inhibitor, was approved for hormone positive metastatic breast cancer.
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And we've come such a long way since then.
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There are additional CDK4-6 inhibitors that have been approved.
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There's various additional endocrine therapies.
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And really in the last five years or so, there's been a revolution of different targetable mutations that we've been able to find and now target.
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So an example of this would be a PIG3CA mutation that we found that we now have drugs that we can use to target.
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Alpaliciv was the first one of these drugs.
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It was approved in May of 2019.
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And then after that, we had development of AKT inhibitors, CERDs for ESR1 mutations, and there's a lot of work being done to find additional mutations that we can target and we can hone in on for what is driving tumor growth, and then really try to get to the source of the growth that's driving that tumor via various mutations.
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Sarah, I just want to break in here and just for our listeners that may not realize that pelviclib is ibrants and alpellisib is pickree.
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Just if we could use those names also for our listeners to know what you're talking about.
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Also, SERDs are selective estrogen receptor degraders.
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Absolutely.
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You got it.
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I'll use some of the trade names too moving forward.
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I think that'll be helpful for the listeners.
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And I also think that in the last several years, and this is really important, there's been a push to try to mitigate the toxicities of the targeted agents so that we can help improve quality of life for our patients.
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So an example of that, we know that AlpaliCib or PICRE has high rates of hyperglycemia.
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So about two-thirds of patients on the trial that approved that were found to have high glucose or hyperglycemia.
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And about a third of the patients were found to have a rash.
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And those things really compromise patients' quality of life.
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So the newest generation of these types of drugs, PI3K inhibitors that are in development, that are actively being developed and being studied in trials, are really aimed at isolating the target and then trying to reduce these other side effects of what we call off-target effects.
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So there's been a big push, and I think just so critical that we try to find drugs that patients can stay on and try to preserve their quality of life.
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And that's another big evolution here.
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We've come a long way.
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We still have such a long way to go, but it's always nice sometimes to take a step back and look at where we've come from.
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And then we also learn a lot from that.
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So as a field, we identify this is an active drug, this is something we can use, but wait, we need to think about it really critically.
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What does this do for our patients truly in the long run?
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And how can we optimize our therapies?
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How can we sequence them?
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How can we try to reconcile all of the different side effects that a patient could be experiencing and what their life would look like on this drug so that we can really find the right sequence, the right means for each and every patient.
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And that might be different for every single patient, depending on a variety of factors, what other conditions they're facing, where they live, what kind of financial implications for different types of drugs that are out there.
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And so I just think as we learn so much from where we've come, this hopefully helps us shape where we're going.
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So one thing that we've started to see in a lot of the phase three trials is combining therapies in a different way.
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And I do like to tell everyone that I combined Pick Ray, Kiscali, and Fastletx back before it was cool.
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But what is it that you're finding that patients are concerned about when you're talking about combining therapies?
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A hundred percent.
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You hit the nail on the head.
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We believe that if we combine therapies, this could be more efficacious because if you're hitting various targets, especially after CDK 4.6 inhibitors, what happens?
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What causes these tumors to develop resistance to the drugs that they're on?
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And this can happen early.
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This can happen later.
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We know in the trials that led to the approval of CDK 4.6 inhibitors, patients on average time before their next progression on scans was about two years.
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So for each of these patients, their tumors are all very different.
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A patient whose tumors progressed within less than two years, it's a very different disease than a patient who was on a CDK4-6 inhibitor for five plus years.
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And we have those patients.
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And so all of this helps us inform what we do next.
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And so to your point, Abigail, there's been a lot of push that, okay, if we combine therapies, if we hit various targets.
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And I can talk about a trial that was recently presented that looked at a triplet therapy that combined three very active agents together, but that came with efficacy, but it also came with toxicity.
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And so that's really where we have to think about okay, it's great to combine things, but where are we gonna get the biggest bang for our buck?
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Where are we gonna be able to truly add value to prolonging progression-free survival?
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But actually realistically having our patients be able to stay on these drugs and have some sort of quality of life and try to work towards better quality of life for our patients.
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So combinations are great, but I think that we have to look at each one very critically.
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So were you referring to the innovalisb trial that was presented last year at San Antonio as breaking news and again this year?
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And this is a very interesting first line treatment.
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Maybe we should talk a little bit about that.
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Yeah, absolutely, Victoria.
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So yeah, you're absolutely right.
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It was the Inovo 120 trial, and that actually was really exciting.
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Basically, there was a press release for positive results for the trial, and we were all in San Antonio, and everyone on the planning committee had worked together in a very speedy fashion to be able to present that while everybody was gathered at the San Antonio conference, and then there's been updated results since then, which has been awesome.
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And then there also was a trial called the Victoria One trial that also looked at a triplet.
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But for Inavo, that was looking at our patients who we believe are the patients that have the highest risk tumors.
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I don't ever really like to say highest risk patients.
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It's their tumors, it's their tumors that have the highest risk.
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But really, these are patients who were on endocrine therapy or had recently completed endocrine therapy and they developed metastatic disease.
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In the adjuvant setting, we're talking about the adjuvant setting early stage breast scans.
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You got it, exactly.
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And so these patients were getting their endocrine therapy, and either while they were on it or within 12 months of having finished it, they unfortunately developed metastatic disease or stage four disease.
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So you would know right there, that's pretty aggressive.
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That means that these patients were getting treatment that was theoretically going around their whole body to try to prevent cancer from coming back, and despite that, cancer still came back.
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So there's something about that tumor biology that's very aggressive, unfortunately.
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So what they did is they looked at patients who have the PIC3CA mutations.
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I alluded to that earlier.
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So that's one of the mutations that a patient can have that can drive tumor growth.
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And this can happen after treatment, but more commonly when tumors develop first, they have this mutation.
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It's what we call a truncal mutation.
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And really what that means is at the genesis of the tumor, when the tumor was born, this is more common for patients to either have this mutation or not.
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I believe it's about 40% of patients that can have this mutation.
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And so what they did is they identified these patients that have this mutation and they gave them three agents.
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And the new agent was in evolution.
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So it's a PI3K alpha isoform inhibitor.
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So it's very specific against this mutation.
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And then when combined with the Ibrands and with fulvestrant, it actually improved the amount of time the patients had before the next treatment that they needed.
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And then actually, we got some updated results this past year that it resulted in patients living longer.
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And so that's overall survival.
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In general, we end up needing to wait a long time with all of these new trials to get overall survival.
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So the fact that we have overall survival data on this group of patients already tells you right there that this is a very aggressive tumor group that we're treating.
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And so at this point, this is very much something that we're adopting in practice.
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And we really encourage every provider that is seeing patients to try to do profiling or mutational analysis up front so that we can see if this is a treatment option for those patients.
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But I will caveat that it's approved in a very specific fashion and it should be given the way the label is evaluating it.
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So, not for patients, for example, who developed de novo disease and they never had gotten endocrine therapy to begin with.
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It wasn't looked at in that fashion.
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There are trials that are looking at inovolisive in other ways.
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But really, this is how the trial was studied and this is how the drug was approved, just as you said, Victoria, as patients were getting endocrine therapy in the early stage setting.
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That's the medication, though, that there was a pretty high incidence of stomatitis, right?
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So controlled the hyperglycemia, not so much of the rash, but the stomatitis, I think, was pretty significant, a grade three.
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Yes, you're right.
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And hyperglycemia as well.
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And there's a lot more data that's coming out and anecdotal experience from folks that are using these drugs, and especially in the community.
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Because if you think about it, these patients who are on trial, they're fit enough to be able to go on trial.
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They're able to get to a center where there is a trial offered, and there's a number of factors that plays into a patient group that's on clinical trial.
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So then when you institute that into the community and widespread use, you can see slight differences there.
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Because there's a lot of different things.
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We have lots of patients who are faced with diabetes, especially in the United States, and it's important to think about that if that's a side effect that we're experiencing.
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Now, in the trial, they did have cutoffs for hemoglobin A1C, and that is important here.
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But really, to your point, Abigail, stomatitis, so mouth ulcers, being on top of that, and then hyperglycemia, and then also there was some rash there too.
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This regimen is tough, but at the same time, sometimes people think that this is the first line.
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So these people who come into the first line treatment are still pretty healthy overall for the most part.
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So if there were time to go aggressive, this would be it.
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So let's talk a little bit about Victoria, shall we?
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And you know.
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It warms my heart to talk about Victoria.
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I will say, I feel like in the field of breast cancer, we do come up with some pretty cool names and ones that are easier to remember.
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I think my colleagues who are practicing in other tumor groups will comment on that that we're quite creative with our names.
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So definitely love the Victoria trial.
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And I'll briefly step back to this is what we were talking about earlier with triplet therapies, right?
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So if we feel strongly that a triplet's going to work, and not only does it allow patients to have more time before they progress again, but it actually allows them to live longer.
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This is where we do our risk-benefit analysis and there's a trade-off there.
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But it's also so important to make sure that both our patients and all providers who are using these drugs feel empowered and educated on how to act ahead, how to try to prevent toxicities, how to counsel their patients on it, and how to think about these things, right?
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And then not just incorporating uh pharmaceutical type interventions, so lifestyle interventions that we should be able to talk about with our patients and other strategies that they can use at home because I think everybody is motivated to.
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We just have to be able to talk about it.
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And that's where we have to weigh things out.
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But Victoria, so this was a really exciting trial.
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It was presented first, as I mentioned, in Europe this past year, 2025.
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So this was evaluating a drug that we call getatolisin.
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Can we just say that the way that they develop names?
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These names are so hard to pronounce.
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I realize that it'll be the same.
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So alpella sib, sib, getolisib, right?
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We know that it's in that PI3 kinase pathway class, but they're still so hard to say.
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You're absolutely right.
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And there's so many more that are coming out.
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I think when Vab Degastret was first published, for example, that's another one.
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The mouthful.
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Everyone was like, how do we say this drug name?
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We definitely appreciate an easier way to be able to identify these drugs.
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But yeah, so Victoria was evaluating a novel drug called get a tolecid, and this is a PAM pathway inhibitor.
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So, what does that mean?
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So we do know that as I mentioned before, there's the PI3K pathway, and that's one pathway that tumors can utilize to enhance their tumor growth along with the mTOR pathway and AKT.
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So these things all work in sync.
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And so this drug is a PAM pathway inhibitor.
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So it hits the full pathway.
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Although I'll caution, it's an IV drug.
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So this is a trial that's looking at combining the getatolis of the IV drug with Ibrands and fulvestrant.
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So here you have an intra drug, you have an oral drug, and you have an IV drug.
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All right, so that's what's going on here, right?
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But actually, it's a very smartly designed study.
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They have two different studies.
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One was looking at a group of patients that do not have a PIC3CA mutation, and then those that did have a PIC3C mutation.
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And the results that were presented so far were the patients that do not have a PIC3CA mutation.
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And so within that, there were three cohorts of patients.
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There was one group of patients who received all three drugs, the getta tollacib, the Ibrands, and the fulvestrant.
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The second group received the getta tolacib and the fulvestrant.
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And then the last group received fulvestrant alone.
00:20:56.000 --> 00:21:02.400
And there's a lot of questions here because really there was a group of patients who received only one drug.
00:21:03.039 --> 00:21:05.599
And back then, that was standard of care.
00:21:05.839 --> 00:21:07.200
That's what we were doing for our patients.
00:21:07.279 --> 00:21:08.480
That's what we had available.
00:21:08.640 --> 00:21:18.079
And this is a problem that we're running into as we're getting readouts for clinical trials, is that what we were doing back then is not necessarily what we're doing now.
00:21:18.240 --> 00:21:34.400
This is something that, you know, as the paradigm of hormone-positive breast cancer and really all areas of breast cancer, as we're shifting our standard of care, the control arm or the arm that's getting one specific type of treatment, which at the time was the standard, ends up changing.
00:21:34.559 --> 00:21:41.440
What's nice about this trial is that they did allow for patients who progressed to then cross over or switch to the other arms.
00:21:41.599 --> 00:21:43.039
So that's a positive thing.
00:21:43.200 --> 00:21:48.960
The other thing to mention is that this trial, along with all the other trials that we've talked about, these are global trials.
00:21:49.039 --> 00:21:53.920
So they're looking across the world and they're looking at patients in various countries.
00:21:54.079 --> 00:21:58.960
And that's also really important because the standard is different in all of these countries.
00:21:59.119 --> 00:21:59.759
What's approved.
00:22:00.480 --> 00:22:07.680
What's not approved, what investigators and clinicians are able to get for their patients versus not be able to give.
00:22:07.839 --> 00:22:12.880
And all of these things impact the results of a clinical trial and how we think about it.
00:22:13.039 --> 00:22:24.000
But nonetheless, the triplet combination resulted in an improvement in the progression-free survival for these patients without a PIG 3CA mutation.
00:22:24.319 --> 00:22:36.640
The updated results from the San Antonio Breast Conference this year, I believe, showed, if I remember correctly, it was about 12.4 months compared to 1.9 months with the fulvestrin.
00:22:36.799 --> 00:22:38.319
And what does this tell us here?
00:22:38.640 --> 00:22:45.519
One, we know that single agent endocrine therapy, like fulvestrin alone, is not sufficient.
00:22:45.759 --> 00:22:47.119
We can't do this anymore.
00:22:47.359 --> 00:22:56.160
Our single agent endocrine therapies that are approved, which we touched on before, the CERDs, that's for a specific patient population.
00:22:56.400 --> 00:22:59.599
But beyond that, we know combinations work better.
00:22:59.680 --> 00:23:02.400
And what we need to do is find the right combination.
00:23:02.559 --> 00:23:07.359
The great data, a lot of questions on the IV use, how practical that is.
00:23:07.519 --> 00:23:10.559
Maybe it is practical for some patients, maybe it's not.
00:23:10.720 --> 00:23:13.920
And so that really has to be considered when we take all of this into account.
00:23:14.000 --> 00:23:15.759
But again, very exciting data.
00:23:15.920 --> 00:23:17.680
I think we're moving forward.
00:23:23.599 --> 00:23:33.920
Before we continue, here is some quick context on why the updated Victoria One results from ASCO 2026 are such a big deal.
00:23:34.240 --> 00:23:43.119
Get a Tolus works by shutting down the entire growth signaling pathway that PIC3CA mutant tumors rely on.
00:23:43.279 --> 00:23:46.640
Not just one part of it, but the whole chain.
00:23:46.880 --> 00:23:58.400
In the Victoria One trial, it was tested in patients whose cancer had already grown through a CDK4-6 inhibitor and who had a PIC3CA mutation driving their tumor.
00:23:58.960 --> 00:24:00.559
The numbers were impressive.
00:24:00.880 --> 00:24:07.440
Patients on the getadolisp triplet went nearly 11 months before their cancer progression.
00:24:07.680 --> 00:24:10.640
The doublet hit just over 11 months.
00:24:10.880 --> 00:24:17.920
Compare that to five and a half months with alpelicip plus fulvestrin, the current standard.
00:24:18.160 --> 00:24:24.319
Both combinations basically doubled the time patients had before needing their next treatment.
00:24:24.880 --> 00:24:27.279
And here is the other big win.
00:24:27.440 --> 00:24:31.200
Alpelicip has always been tough on blood sugar.
00:24:31.519 --> 00:24:43.519
Get a tellycip caused far fewer severe blood sugar spikes, which means patients may actually be able to stay on it longer, better results, and easier to tolerate.
00:24:43.680 --> 00:24:46.799
That's what has oncologists paying attention.
00:24:47.119 --> 00:25:00.079
I can just very briefly touch on there is an ongoing trial called the Elevate trial that's actually looking at several different combinations of medications and it's constantly reading out.
00:25:00.160 --> 00:25:05.519
So at San Antonio, there were two combinations that were shared with us that also looked promising.
00:25:05.599 --> 00:25:11.440
And so while that's a little bit earlier, it's a phase two trial, it also is giving us a lot of data on combinations.
00:25:11.519 --> 00:25:16.400
And as we go along, we're looking at safety and tolerability along with efficacy.
00:25:17.200 --> 00:25:18.720
So why don't we do that?
00:25:18.880 --> 00:25:23.920
Why don't we dive into this new exciting world of SERDs?
00:25:24.319 --> 00:25:28.559
Gamasestrin, alocestrin, gerodestrin.
00:25:29.039 --> 00:25:29.599
What else?
00:25:29.759 --> 00:25:30.160
Which one?
00:25:30.319 --> 00:25:31.599
Imlunestrin.
00:25:32.880 --> 00:25:33.680
You're so right.
00:25:33.839 --> 00:25:34.880
Pick your favorite one.
00:25:34.960 --> 00:25:35.680
There's so many.
00:25:35.759 --> 00:25:38.400
They're out there, many others that are under development.
00:25:38.559 --> 00:25:40.720
And Abigail touched on this before.
00:25:40.880 --> 00:25:42.079
What are CERDs?
00:25:42.480 --> 00:25:48.079
So, as she mentioned, just perfectly mentioned, these are selective estrogen receptor graders.
00:25:48.240 --> 00:25:51.279
And these are a novel form of endocrine therapy.
00:25:51.440 --> 00:26:04.960
So, unlike the previous generation of endocrine therapies, which either blocked the production of estrogen, or they, for example, competitively inhibited receptor activation, these SERDs directly degrade the receptor.
00:26:05.119 --> 00:26:14.400
And this type of mechanism, it allows SERDS to overcome one of the key resistance mechanisms that can develop to, for example, aromatase inhibitors.
00:26:14.480 --> 00:26:23.119
And that is what I briefly touched on before, which is an ESR1 mutation, in which the receptor is constituently activated.
00:26:23.200 --> 00:26:26.000
So it's constantly on, it's constantly running.
00:26:26.160 --> 00:26:31.440
And so if you can degrade that receptor effectively, that's one way to target this.
00:26:31.680 --> 00:26:47.279
We do know that these SERDs are still active in patients who don't necessarily have an ESR1 mutation, or that ESR1 mutations are driving the cancer or leading to the growth of tumors, but on their own, they're not sufficient.
00:26:47.359 --> 00:26:50.160
And this is again where the combination therapy comes in.
00:26:50.319 --> 00:27:10.799
But nonetheless, the SERDs are very exciting, and we have two that are out there in the metastatic setting that have been approved for those patients that have ESR1 mutations and multiple other SERDs that are being studied in combination with other targeted therapies like CDK4-6 inhibitors, which are all very exciting.
00:27:11.119 --> 00:27:22.079
There also was presented this year the use of cambasestrin, Victoria, you mentioned this, which was studied in the Serena 6 trial presented at ASCO this past year, 2025.
00:27:22.319 --> 00:27:24.960
This was a really novel type of clinical trial.
00:27:25.039 --> 00:27:45.279
So these are patients who were already on their first line of treatment, the aromatase inhibitor and CDK4-6 inhibitors, and they looked at what we call circulating tumor DNA, so fragments of DNA that was shed by tumors into the bloodstream to evaluate for ESR-1 mutations showing up in the blood.
00:27:45.440 --> 00:28:14.799
And they were looking to see, this trial was looking to see that if you switch the aromatase inhibitor to the CERD and keep the CDK4-6 inhibitor going, versus if you continue the aromatase inhibitor as those patients were receiving with the CDK4-6 inhibitor until the scans picked up progression, which is the way that we treat our patients most commonly right now, doesn't make a difference in how long patients have until their next progression.
00:28:15.039 --> 00:28:19.359
What we did find is that medium progression-free survival, it was prolonged.
00:28:19.440 --> 00:28:20.559
It certainly was.
00:28:20.799 --> 00:28:23.359
However, there's a lot of caveats here.
00:28:23.599 --> 00:28:31.440
We didn't really quite identify, at least not yet, that if we switch treatments, are patients really living longer?
00:28:31.599 --> 00:28:38.960
Or are we just moving our treatments earlier and using up some of our good treatments earlier than they need to be used up?
00:28:39.119 --> 00:28:41.119
And that still remains to be seen.
00:28:41.359 --> 00:28:47.279
I think CT DNA or circulating tumor DNA is very cool technology.
00:28:47.440 --> 00:28:48.640
I think we're getting there.
00:28:48.799 --> 00:28:52.000
I don't know that we're quite there, but we're getting there.
00:28:52.160 --> 00:29:05.759
I really believe in the next three to five years, we hopefully will be there in really detecting at a low level these mutations in the blood and then trying to figure out how exactly we act on them.
00:29:06.000 --> 00:29:08.960
And then really, it gets more complicated than that.
00:29:09.119 --> 00:29:14.559
Of all patients who have ESR1 mutations picked up in their blood, do all of them need to switch?
00:29:14.720 --> 00:29:16.240
Maybe only some of them need to switch.
00:29:16.400 --> 00:29:21.279
We have to try to hone in on really personalizing this type of strategy.
00:29:21.359 --> 00:29:22.240
It's a great strategy.
00:29:22.319 --> 00:29:29.680
It's really unique, it's really novel, but it may only be important for us to do this for some patients, maybe not all patients.
00:29:29.839 --> 00:29:33.920
And that's really where we need to go, and that's where I believe that we're headed.
00:29:34.240 --> 00:29:42.559
Sarah, you are at a wonderful institution who is very much looking at those biomarker testing, looking at CT DNA.
00:29:42.799 --> 00:29:50.160
And that's great for people who are in an academic setting or treated at one of these wonderful comprehensive cancer centers.
00:29:50.319 --> 00:30:02.079
But we know a large majority of people living with cancer are treated in a community setting, in a rural setting, often with an oncologist who may not specialize in breast cancer.
00:30:02.319 --> 00:30:04.720
And so we're talking about these great tests.
00:30:04.799 --> 00:30:07.440
You talked about biomarker testing early on.
00:30:07.599 --> 00:30:09.920
You talked about CT DNA testing.
00:30:10.160 --> 00:30:25.920
What is the language that patients can be using to ask their doctors for the testing that will give them these targets or give them more options for treatment for those people whose doctors may not be up on all the tests for all the different kinds of cancer?
00:30:26.079 --> 00:30:27.599
Because not everybody can do that.
00:30:27.839 --> 00:30:29.599
You're exactly right, they can't.
00:30:29.759 --> 00:30:34.880
So a lot of these providers in the community, they're seeing every type of cancer.
00:30:34.960 --> 00:30:41.920
And I'm so lucky that I get to specialize really in breast cancer, and then I also treat patients with gynecologic cancer.
00:30:42.079 --> 00:30:44.960
But a lot of providers they don't have that luxury.
00:30:45.119 --> 00:30:49.839
They're keeping up to date, as you mentioned, on so many different types of cancers.
00:30:50.000 --> 00:31:00.079
And they're, for example, walking down a hallway and they're seeing a patient that has a blood cancer, and then they're seeing a patient that has lung cancer, and they're seeing a patient that has a GI cancer and breast cancer.
00:31:00.160 --> 00:31:04.799
And while the field of breast cancer is moving fast, so are all these other tumors.
00:31:04.880 --> 00:31:07.920
And so, how do they truly keep track of all of this?
00:31:08.160 --> 00:31:18.319
Now at Sarah Canon, we are predominantly academic in the sense that we have investigators here who get the chance to do research and also see patients.
00:31:18.559 --> 00:31:22.720
The network is fully integrated within the community, which has been so awesome.
00:31:22.880 --> 00:31:30.480
So we've got sites that are all over the community and we work with local community doctors to try to enroll patients onto clinical trials.
00:31:30.559 --> 00:31:37.119
And through that, it's been great because we get to work with clinicians who treat all types of cancers.
00:31:37.279 --> 00:31:48.799
And if these providers are able to work with their patients who want to go on clinical trials and educate their patients on clinical trials, they get to use these drugs earlier than sometimes they're approved.
00:31:48.880 --> 00:31:51.200
And so then they feel more comfortable with using it.
00:31:51.359 --> 00:32:00.079
They're able to really teach their other colleagues who they work with on how to mitigate side effects or how to act ahead or how things were instituted.
00:32:00.640 --> 00:32:14.240
But for any patient who's interested in learning about clinical trials, there's so many patient advocacy groups that are out there that really partner with a lot of these institutions in trying to teach what's out there, what's available.
00:32:14.480 --> 00:32:18.720
If there's any message I could give to any patient about this, it's ask questions.
00:32:18.880 --> 00:32:19.839
Ask your doctors.
00:32:20.000 --> 00:32:23.599
You can always ask, what were the latest clinical trials that were presented?
00:32:23.839 --> 00:32:24.880
Could we look at it together?
00:32:25.039 --> 00:32:26.640
Could we explore what's out there?
00:32:26.799 --> 00:32:37.680
Or would you be willing to connect with any scientist that you know that maybe is a little bit more up to date on the breast cancer trials and maybe see if any of them would be options for me.
00:32:37.920 --> 00:32:46.000
But also, there's so many amazing resources that are geared to patient education because I just think our breast cancer patients, they're so savvy.
00:32:46.160 --> 00:32:48.480
They do their research, they know their stuff.
00:32:48.720 --> 00:32:49.839
Not everyone can.
00:32:50.000 --> 00:32:55.839
Some people don't have the chance to, some people don't have the means to, some people don't have the time to.
00:32:56.000 --> 00:33:00.559
And that's where really the partnership between a patient and a provider is so sacred.
00:33:00.720 --> 00:33:06.880
And I think that anyone I'm hoping is feeling encouraged and empowered to just ask their doctor questions.
00:33:07.039 --> 00:33:14.400
If they don't know exactly why they're getting what they're getting, what else they could be getting, don't be afraid to ask your doctor.
00:33:14.559 --> 00:33:17.359
That's why we're here, and that's ultimately what we're here to do.
00:33:17.440 --> 00:33:19.440
And so definitely encourage that.
00:33:21.519 --> 00:33:32.640
So we touched upon SERDs, and I think it's important to mention that even though CERDs are novel, we already have one CERD that we've been using for a very long time.
00:33:32.720 --> 00:33:35.759
It's pulvestrin or Fazilodex.
00:33:36.000 --> 00:33:42.640
So these are new novel oral SERDs, but they are not novel classic drugs.
00:33:47.359 --> 00:33:51.200
And speaking of gyrodestrin, or gerodestrin, you pick.
00:33:51.599 --> 00:33:56.799
We just got major news from ESCOTA 2026 that is worth a quick pause.
00:33:57.039 --> 00:34:00.960
Gerodestrin is a next generation oral hormone therapy.
00:34:01.119 --> 00:34:12.320
The idea being it could replace letrozole as the estrogen blocking partner alongside a CDK4-6 inhibitor, like polbocyclip, or Ibrands in the first-line setting.
00:34:12.559 --> 00:34:16.480
The phase three persevered trial put that to the test.
00:34:16.719 --> 00:34:22.719
Giridestrin plus polvocyclip versus the current standard of letrozole plus polvocyclip.
00:34:22.960 --> 00:34:24.960
Here is the honest read on the results.
00:34:25.119 --> 00:34:33.440
Patients on juridestrin went about 33 months before their cancer progressed, compared to 28 months on the standard arm.
00:34:33.679 --> 00:34:35.280
That's a five-month difference.
00:34:35.360 --> 00:34:39.840
And it's real, but it didn't cross the threshold for statistical significance.
00:34:40.079 --> 00:34:45.280
In clinical trial terms, that means we can definitely call it superior.
00:34:45.599 --> 00:34:47.920
Not a practice changer today.
00:34:48.159 --> 00:34:51.039
But here is the takeaway that often gets buried.
00:34:51.280 --> 00:34:57.360
Patients on both arms are now averaging nearly three years before needing to switch treatments.
00:34:57.519 --> 00:35:01.920
That's a remarkable benchmark for first-line metastatic breast cancer.
00:35:02.000 --> 00:35:05.519
And it tells us just how far this disease has come.
00:35:05.920 --> 00:35:08.159
Jodesterin isn't done.
00:35:08.480 --> 00:35:12.719
Longer follow-up and overall survival data are still to come.
00:35:13.039 --> 00:35:17.280
Okay, so let's talk about things other than CERDs.
00:35:17.360 --> 00:35:18.800
And there are many of those, right?
00:35:19.119 --> 00:35:22.719
There are CRANs and Protax, and what else is there?
00:35:23.280 --> 00:35:24.000
You got it.
00:35:24.159 --> 00:35:26.239
There are CRANs, there's Protax.
00:35:26.559 --> 00:35:27.039
CERMS.
00:35:27.199 --> 00:35:28.480
There's even a novel CERM.
00:35:28.639 --> 00:35:30.639
I've been on tamoxifen for 20 years.
00:35:30.800 --> 00:35:36.639
So this is interesting to see a new tamoxifen-like agent coming to market.
00:35:37.280 --> 00:35:37.760
Yep.
00:35:38.000 --> 00:35:40.800
This is what we call at this point our word salad.
00:35:40.880 --> 00:35:44.400
We have so many different types of novel endocrine therapies.
00:35:44.559 --> 00:35:51.119
Just as you said, we have a new generation of the selective estrogen receptor modulators.
00:35:56.159 --> 00:36:01.840
Before Sarah gives her own explanation, here is a quick breakdown of what a protuc actually is.
00:36:02.000 --> 00:36:06.960
Think of a protock like a seek and destroy mechanism for the estrogen receptor.
00:36:07.199 --> 00:36:13.519
Instead of just blocking it, the drug marks it for destruction using the cell's own internal disposal system.
00:36:13.760 --> 00:36:20.079
Once the receptor is tagged, it gets broken down, and then the drug gets recycled to do it again.
00:36:20.559 --> 00:36:26.719
That's what makes a dagostone different from a standard estrogen receptor blocker.
00:36:26.960 --> 00:36:43.440
On May 1st, 2025, the FDA approved a pedestrian for this exact indication, making it the third oral endocrine agent approved for ESR1 mutated metastatic breast cancer, joining LS estrant and immunestrin.
00:36:43.840 --> 00:36:54.239
And the tolerability profile is notably cleaned, low rates of nausea, minimal diarrhea, and a small, non-clinically significant QTC signals.
00:36:55.199 --> 00:37:01.840
A baseline EKG is recommended, but ongoing cardiac monitoring is not required.
00:37:02.159 --> 00:37:03.679
The protex, what are those?
00:37:03.760 --> 00:37:06.239
Those are proteolysis targeting chimera.
00:37:06.800 --> 00:37:07.840
Say it five times.
00:37:08.159 --> 00:37:09.599
Yep, yep, the protex.
00:37:09.679 --> 00:37:11.599
That's the BEP dagastriant that we talked about.
00:37:11.679 --> 00:37:16.079
That's one of the drugs that tries to more potently degrade the ER receptor.
00:37:16.159 --> 00:37:20.719
There's the CERANs, those are complete estrogen receptor antagonists.
00:37:20.800 --> 00:37:25.119
So what they do is they block multiple domains of the receptor to degrade it.
00:37:25.280 --> 00:37:28.320
So there's just so many exciting new drugs out there.
00:37:28.480 --> 00:37:35.840
But what we need to figure out is what we were chatting about earlier, which ones are the most effective for which patients and in what combination.
00:37:36.000 --> 00:37:38.800
And so that's really what's being studied now.
00:37:39.119 --> 00:37:39.519
All right.
00:37:39.679 --> 00:37:41.519
We have taken up a lot of your time.
00:37:41.679 --> 00:37:43.119
Well, we say goodbye.
00:37:43.360 --> 00:37:45.119
A difficult question for you.
00:37:45.280 --> 00:37:45.519
Yeah.
00:37:45.679 --> 00:37:48.480
So do you have an algorithm now?
00:37:48.719 --> 00:37:49.920
So what happens?
00:37:50.079 --> 00:37:52.320
Okay, you know what to do on the first line.
00:37:52.400 --> 00:37:53.360
Not quite, actually.
00:37:53.519 --> 00:37:54.559
There are options there.
00:37:54.800 --> 00:37:58.159
A lot of these drugs have not been approved yet.
00:37:58.239 --> 00:38:02.480
They're not FDA approved, they're only available in the clinical trial setting.
00:38:02.719 --> 00:38:13.280
But assuming they are going to be approved, what's the new algorithm for treating HR positive HER2 negative MBC population?
00:38:13.679 --> 00:38:21.760
In my mind, this is constantly evolving and it's evolving on a monthly, if not sometimes weekly basis.
00:38:22.000 --> 00:38:27.440
But just as you said, I really try to think about each patient in front of me individually.
00:38:27.599 --> 00:38:29.280
So there's a number of factors.
00:38:29.440 --> 00:38:37.119
Number one is doing what we mentioned, which is profiling their tumors, identifying which mutations do they have.
00:38:37.199 --> 00:38:52.639
Because even if they don't necessarily have a ESR1 mutation or a PIG3CA mutation, or we didn't touch on this, but a BRCA mutation, or the very rare mutations like NTREC fusions, for example, that opens up another treatment line.
00:38:52.719 --> 00:39:01.039
If they don't have one of those, it's still really important to know what mutations do they have, because that can tell you a little bit about their tumor.
00:39:01.280 --> 00:39:09.280
So doing that, also trying to look at how long was a patient on their first treatment, because that can give you a little bit of an idea.
00:39:09.440 --> 00:39:27.760
If they were on the first treatment for a long time, maybe they have endocrine sensitive disease, or the estrogen receptor is still playing an active role in the growth of a tumor versus a patient's tumor who's endocrine resistant, meaning their tumor found lots of other ways to grow around the estrogen receptor.
00:39:27.920 --> 00:39:29.199
So I think that's important.
00:39:29.440 --> 00:39:33.599
I think how a patient did on their first line treatment is important.
00:39:33.760 --> 00:39:35.920
What side effects did they experience?
00:39:36.079 --> 00:39:39.599
What are things to think about as we pick our next line of treatment?
00:39:40.000 --> 00:39:42.960
Also trying to think about what is the best thing for our patient.
00:39:43.119 --> 00:39:44.480
Do they live really far away?
00:39:44.639 --> 00:39:48.400
And trying to think about an oral regimen versus an IV regimen.
00:39:48.559 --> 00:39:52.719
And then what quality of life factors are important to our patient?
00:39:52.880 --> 00:40:01.599
If it's really important for that patient to be able to travel, then I wouldn't necessarily jump to an IV drug unless I felt like it was really needed for that patient.
00:40:01.679 --> 00:40:09.760
And then I would talk through that with that patient versus picking an oral drug, intramuscular drug, the fulvestrant, like you mentioned, depending on what they received in the first line.
00:40:09.840 --> 00:40:12.880
So there's just so many factors that go into it.
00:40:12.960 --> 00:40:17.199
But I think that the first thing is look at the patient in front of you.
00:40:17.360 --> 00:40:18.320
What did they receive?
00:40:18.480 --> 00:40:19.760
How long do they receive it for?
00:40:19.920 --> 00:40:21.679
What other conditions are they facing?
00:40:21.840 --> 00:40:23.360
What are their lifestyle factors?
00:40:23.599 --> 00:40:26.400
What is a priority for that patient at that time?
00:40:26.559 --> 00:40:29.920
Because that can change as well over a patient's lifespan.
00:40:30.079 --> 00:40:37.360
What certain life factors and what things are happening in their life outside of their cancer can certainly help you decide what you're doing next.
00:40:37.519 --> 00:40:39.840
And then of course, where are the sites of disease?
00:40:40.000 --> 00:40:42.159
Is this disease that's only in the bone?
00:40:42.320 --> 00:40:44.400
Is this disease that's spread to the liver?
00:40:44.559 --> 00:40:48.639
Is this involving the lungs, the bone, the liver involving all of these?
00:40:48.800 --> 00:40:50.000
Is the brain involved?
00:40:50.159 --> 00:40:52.400
These are all things that are really important to consider.
00:40:52.559 --> 00:40:55.599
I think also the subtype of breast cancer is important.
00:40:55.760 --> 00:40:58.400
We know our two most common is ductal and lobular.
00:40:58.480 --> 00:41:05.280
We didn't really go into the nuances there, but these are two different types of breast cancer, especially in the hormone-positive space.
00:41:05.360 --> 00:41:07.679
And so these are all things that play a role.
00:41:07.840 --> 00:41:13.280
If somebody has a lot of gastric disease, I would be hesitant to use something oral, for example.
00:41:13.440 --> 00:41:16.960
So there's just so many different factors that play into it.
00:41:17.199 --> 00:41:26.400
But starting first with overall survival data, we know that patients live longer with aromatase inhibitors and CDK4-6 inhibitors in the first line.
00:41:26.639 --> 00:41:39.519
Then after that, profiling our patients' tumors, understanding what mutations they have, and then taking into account all of the other factors to decide what is next, and then what is after that is really my approach.
00:41:40.400 --> 00:41:47.440
So basically, this is hard for you guys who specialize in breast cancer.
00:41:47.840 --> 00:41:51.519
What about the community general oncologists?
00:41:51.679 --> 00:41:54.639
How are they going to decide all of this?
00:41:54.880 --> 00:42:00.639
What is the role of AI, in your opinion, given this landscape right now?
00:42:01.039 --> 00:42:01.920
It's a great question.
00:42:02.079 --> 00:42:05.440
I think AI is being used in a lot of different ways.
00:42:05.599 --> 00:42:13.360
I think that providers are learning how to leverage AI, either to learn what the latest data is that's out there.
00:42:13.599 --> 00:42:16.719
We use AI for clinical trial matching sometimes.
00:42:16.880 --> 00:42:25.440
AI is being integrated more in pathologies when we look under the microscope and try to identify what type of cancer is there or what subtype of cancer is there.
00:42:25.599 --> 00:42:33.920
We can try to use AI for imaging, for modeling, and determining what could be there, and then also trying to integrate it with CT DNA monitoring.
00:42:34.079 --> 00:42:37.039
So I think AI is making its way into this.
00:42:37.119 --> 00:42:47.679
And the hope is that AI will help providers be more efficient at their jobs, and it will help because that relationship that I have with my patients is just so sacred.
00:42:47.840 --> 00:42:51.199
It's so special that I hope that never goes away.
00:42:51.440 --> 00:42:54.719
That's my favorite thing about my job, working with my patients.
00:42:54.960 --> 00:42:57.199
So I hope that is there to stay.
00:42:57.280 --> 00:43:02.159
But the other hope is that AI can be used to make our jobs easier.
00:43:02.320 --> 00:43:16.000
And this busy, evolving world that we're in, as there's so many competing efforts on our time and our attention, if we can use AI in the smartest way possible and responsibly, of course, making sure that AI is correct.
00:43:16.159 --> 00:43:21.760
That's what we're honing in on, is that it actually can help us enable us to do an even better job.
00:43:22.159 --> 00:43:28.480
To sum it all up, you're feeling optimistic about the future for this subtype.
00:43:28.800 --> 00:43:32.480
I certainly the most common subtype in breast cancer.
00:43:32.800 --> 00:43:37.679
The most common subtype, 70% of our patients having hormone-positive breast cancer.
00:43:37.920 --> 00:43:44.320
Feeling optimistic about all subtypes, but also in hormone-positive breast cancer, I think we've come a long way.
00:43:44.480 --> 00:43:46.239
I think we have a long way to go.
00:43:46.400 --> 00:43:55.280
I think we're trying to ask the right questions and we're actively trying to address them, whether that's in the lab, whether that's in clinical trials, and we all learn from each other.
00:43:55.440 --> 00:43:58.960
I learn from other investigators, we learn from our patients, learn from us.
00:43:59.039 --> 00:44:00.559
We're all one big community.
00:44:00.719 --> 00:44:07.840
And I really believe, I feel that together, the hope and prayer is that one day we will be rid of this.
00:44:08.000 --> 00:44:11.840
We will eradicate this and this will not be a problem for us anymore.
00:44:12.000 --> 00:44:13.760
I think we're moving closer there.
00:44:13.840 --> 00:44:20.159
I think we still humbly have a way to go, but at least if we're moving in the right direction, it gives us a lot of hope.
00:44:20.480 --> 00:44:23.119
That is such a wonderful way to end.
00:44:23.599 --> 00:44:27.280
Thank you so very much for being here.
00:44:27.440 --> 00:44:30.400
It was such a pleasure to have you with us.
00:44:30.800 --> 00:44:36.159
And I have learned something about you that you also treat gynecological cancer.
00:44:36.800 --> 00:44:41.760
So we need to have you back and talk about sex.
00:44:42.880 --> 00:44:44.400
I would be happy to join you again.
00:44:44.480 --> 00:44:45.039
Absolutely.
00:44:45.280 --> 00:44:46.079
Thank you so much.
00:44:46.159 --> 00:44:55.119
And we'll see you soon when we do the part two, when we talk about HERTU positive MBC.
00:44:55.519 --> 00:44:56.159
Take care.
00:44:56.480 --> 00:44:57.039
You got it.
00:44:57.119 --> 00:44:58.800
Thanks again for having me.
00:45:08.480 --> 00:45:10.800
That wraps up our discussion.
00:45:10.960 --> 00:45:12.320
Here's what we covered.
00:45:12.480 --> 00:45:17.920
The treatment landscape has evolved dramatically with oral SERDs now leading the charge.
00:45:18.239 --> 00:45:28.719
We discussed how CK46 inhibitors remain the first-line backbone and why ESR-1 mutations are a critical biomarker to track progression.
00:45:28.880 --> 00:45:44.000
We explored the new wave of endocrine agents, LSE and luminestrin, and lepiduchestrand, as well as next generation mechanisms like Protex and CERMS, and what distinguishes them from traditional estrogen receptor blockers.
00:45:44.159 --> 00:45:45.039
We heard from Dr.
00:45:45.199 --> 00:45:57.599
Sarah Pramgee about how she approaches treatment decisions in the real world, weighing tumor profiling, priotherapy sites of disease, and each patient's individual lifestyle and priorities.
00:45:57.840 --> 00:46:12.639
And we touched on the emerging role of AI in oncology, from clinical trial matching to pathology and imaging with the hope that technology can support and not replace the sacred patient-physician relationship.
00:46:13.840 --> 00:46:22.480
The bottom line we're in the period of rapid and meaningful progress for the most common subtype of breast cancer.
00:46:22.719 --> 00:46:31.440
The right questions are being asked, the trials are underway, and there is a real reason for optimism and a disclaimer.
00:46:31.760 --> 00:46:38.400
This podcast is intended for educational purposes only and does not constitute medical advice.
00:46:38.639 --> 00:46:45.039
The opinions expressed are those of the speakers and do not represent any institution or organization.
00:46:45.360 --> 00:46:52.079
Treatment decisions should always be made in consultation with a qualified healthcare provider.
00:46:52.480 --> 00:46:59.519
Thank you for being here, and we'll see you next time at Live from Stage Four.
00:46:59.679 --> 00:47:00.559
Goodbye.
00:00:09.839 --> 00:00:12.960
Could cure for cancer be closer than you think?
00:00:13.199 --> 00:00:24.800
Welcome to Life from Stage 4, where MBC takes center stage as we talk to experts, share inspiring stories, break down signs, and shine the spotlight on what matters most.
00:00:25.120 --> 00:00:30.480
Because when it comes down to it, the spot, for us and by us, is all about us.
00:00:36.799 --> 00:00:39.359
Welcome back to Life from Stage 4.
00:00:39.520 --> 00:00:41.200
I'm Victoria Goldberg.
00:00:41.439 --> 00:00:48.640
In the last month, if you've been following along, you know we spent a lot of time, and rightfully so.
00:00:48.960 --> 00:00:52.399
Deep in the weeds of Serena 6 and Cam Zastri.
00:00:52.880 --> 00:00:56.960
Between our patient panel episode, our conversation with Dr.
00:00:57.119 --> 00:00:58.479
Sarah Sammons and Dr.
00:00:58.560 --> 00:01:01.600
Neil Vassan, and everything in between.
00:01:01.920 --> 00:01:05.280
We have really given the story the attention it deserved.
00:01:05.519 --> 00:01:06.799
And it deserved it.
00:01:07.040 --> 00:01:18.719
Using a block test to detect resistance before a scan even shows progression is a genuine paradigm shift, even if the regulatory path is still being sorted out.
00:01:19.040 --> 00:01:23.840
But to understand why all of this matters, it helps to zoom out.
00:01:24.079 --> 00:01:24.400
Dr.
00:01:24.560 --> 00:01:29.280
Erica Hamilton, in her recent interview with Oncology Brothers, put it well.
00:01:29.680 --> 00:01:37.680
For over a decade, our advances in ER-positive HER2-negative breast cancer have come from targeted agents.
00:01:38.000 --> 00:01:47.439
CDK46 inhibitors, PI3, PI3K and AKT inhibitors, but we haven't had a truly novel endocrine backbone since Volvestra.
00:01:48.000 --> 00:01:49.599
This is what has changed.
00:01:49.760 --> 00:01:55.120
We are now in the era of oral CERDs, and the field is moving fast.
00:01:55.519 --> 00:02:08.080
In the past year alone, the docastron, a first in-class product degradator, a different mechanism of action from a CERD, one that flags the estrogen receptor for destruction and recycles itself.
00:02:08.240 --> 00:02:16.639
To do it again, received FDA approval for ESR1 mutated metastatic breast cancer based on the Very TAC2 trial.
00:02:16.960 --> 00:02:18.000
Immunestrin.
00:02:18.960 --> 00:02:37.439
Another oral CERP received FDA approval as a single agent and updated amber 3 data from SCO2026 showed it improved overall survival in ESR1 mutated patients to 35.4 months versus 23.1 months with standard therapy.
00:02:37.599 --> 00:02:42.719
And when combined with IBRANDS, progression-free survival nearly doubled.
00:02:42.960 --> 00:02:53.439
The field is now seriously asking whether CERT targeted agent combination should become the new standard of care for most PSR1 mutated patients.
00:02:54.000 --> 00:02:55.759
And that is exactly the question.
00:02:56.000 --> 00:03:07.919
There are now multiple oral CERDs, pro-TAC, new CERMS, new serums, combinations being explored across lines of therapy, trials in the first-line setting, adjuvant trials.
00:03:08.319 --> 00:03:12.879
The landscape has become rich and frankly very complex.
00:03:13.280 --> 00:03:18.240
We have spent our last few episodes focused on Serena 6 and Kamisestrin.
00:03:18.639 --> 00:03:21.599
Today it is time to talk about everything else.
00:03:21.919 --> 00:03:26.080
Joining me, my co-host and friend Abigail Johnston and Dr.
00:03:26.159 --> 00:03:31.120
Sarah Pramji, a medical oncologist from Sarah Canon in Nashville.
00:03:31.360 --> 00:03:35.439
And so, without further ado, let's get started.
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Abigail Johnston is with me.
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I so love having her with us.
00:03:59.360 --> 00:04:02.879
And now we have a new friend that we just met.
00:04:03.039 --> 00:04:03.759
Her name is Dr.
00:04:03.919 --> 00:04:04.960
Sarah Premji.
00:04:05.759 --> 00:04:20.160
And we're here to talk about the fast and furious development in the space of metastatic breast cancer for HR-positive HER2 negative population.
00:04:20.720 --> 00:04:25.680
And Sarah, please introduce yourself and tell us about yourself.
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Absolutely.
00:04:26.879 --> 00:04:28.399
Thanks so much for having me.
00:04:28.639 --> 00:04:32.240
So, just as Victoria mentioned, my name is Sarah Premje.
00:04:32.800 --> 00:04:39.120
I serve as the assistant director of breast cancer research at Sarah Canon in Nashville, Tennessee.
00:04:39.279 --> 00:05:03.040
I graduated from Mayo Clinic in Rochester, Minnesota, where I discovered my love of breast cancer and got a chance to work on some really cool projects over there that I'm continuing on here, along with my role in serving as the principal investigator on several different trials, looking at early phase development of novel therapeutics in breast cancer and also in the phase three space.
00:05:03.199 --> 00:05:07.759
So happy to be here, happy to provide any insights, and thanks again for having me.
00:05:08.160 --> 00:05:09.120
Absolutely.
00:05:09.360 --> 00:05:11.120
We honored to have you with us.
00:05:11.199 --> 00:05:11.920
And Dr.
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Erica Hamilton has introduced us, and we love Dr.
00:05:16.720 --> 00:05:17.920
Erica Hamilton.
00:05:18.160 --> 00:05:20.079
So thank you for being here.
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She is a wonderful mentor.
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I'm so lucky to learn and get to work with her.
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Yes, yes, we feel the same way.
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So let's start.
00:05:35.600 --> 00:05:47.360
It will be important for us to start from the beginning and actually talk a little bit about the landscape and what is currently happening with this space.
00:05:47.680 --> 00:05:48.720
Yeah, absolutely.
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So I feel like hormone-positive breast cancer, it's evolved rapidly and really over the past decade or so has revolutionized.
00:05:58.480 --> 00:06:10.800
So we do know that in early 2015, I think it was February of 2015, palbocyclib, our first CDK4-6 inhibitor, was approved for hormone positive metastatic breast cancer.
00:06:10.959 --> 00:06:13.519
And we've come such a long way since then.
00:06:13.680 --> 00:06:17.279
There are additional CDK4-6 inhibitors that have been approved.
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There's various additional endocrine therapies.
00:06:20.160 --> 00:06:29.439
And really in the last five years or so, there's been a revolution of different targetable mutations that we've been able to find and now target.
00:06:29.600 --> 00:06:36.480
So an example of this would be a PIG3CA mutation that we found that we now have drugs that we can use to target.
00:06:36.720 --> 00:06:39.439
Alpaliciv was the first one of these drugs.
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It was approved in May of 2019.
00:06:42.079 --> 00:07:02.399
And then after that, we had development of AKT inhibitors, CERDs for ESR1 mutations, and there's a lot of work being done to find additional mutations that we can target and we can hone in on for what is driving tumor growth, and then really try to get to the source of the growth that's driving that tumor via various mutations.
00:07:02.800 --> 00:07:12.160
Sarah, I just want to break in here and just for our listeners that may not realize that pelviclib is ibrants and alpellisib is pickree.
00:07:12.319 --> 00:07:17.040
Just if we could use those names also for our listeners to know what you're talking about.
00:07:17.279 --> 00:07:21.759
Also, SERDs are selective estrogen receptor degraders.
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Absolutely.
00:07:22.959 --> 00:07:23.519
You got it.
00:07:23.680 --> 00:07:25.759
I'll use some of the trade names too moving forward.
00:07:25.839 --> 00:07:27.839
I think that'll be helpful for the listeners.
00:07:28.079 --> 00:07:41.120
And I also think that in the last several years, and this is really important, there's been a push to try to mitigate the toxicities of the targeted agents so that we can help improve quality of life for our patients.
00:07:41.199 --> 00:07:48.319
So an example of that, we know that AlpaliCib or PICRE has high rates of hyperglycemia.
00:07:48.639 --> 00:07:56.800
So about two-thirds of patients on the trial that approved that were found to have high glucose or hyperglycemia.
00:07:56.959 --> 00:08:00.079
And about a third of the patients were found to have a rash.
00:08:00.399 --> 00:08:03.759
And those things really compromise patients' quality of life.
00:08:03.920 --> 00:08:20.560
So the newest generation of these types of drugs, PI3K inhibitors that are in development, that are actively being developed and being studied in trials, are really aimed at isolating the target and then trying to reduce these other side effects of what we call off-target effects.
00:08:20.720 --> 00:08:28.639
So there's been a big push, and I think just so critical that we try to find drugs that patients can stay on and try to preserve their quality of life.
00:08:28.720 --> 00:08:30.720
And that's another big evolution here.
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We've come a long way.
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We still have such a long way to go, but it's always nice sometimes to take a step back and look at where we've come from.
00:08:39.279 --> 00:08:41.279
And then we also learn a lot from that.
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So as a field, we identify this is an active drug, this is something we can use, but wait, we need to think about it really critically.
00:08:48.480 --> 00:08:52.000
What does this do for our patients truly in the long run?
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And how can we optimize our therapies?
00:08:54.639 --> 00:08:56.240
How can we sequence them?
00:08:56.480 --> 00:09:09.759
How can we try to reconcile all of the different side effects that a patient could be experiencing and what their life would look like on this drug so that we can really find the right sequence, the right means for each and every patient.
00:09:09.840 --> 00:09:22.559
And that might be different for every single patient, depending on a variety of factors, what other conditions they're facing, where they live, what kind of financial implications for different types of drugs that are out there.
00:09:22.799 --> 00:09:28.879
And so I just think as we learn so much from where we've come, this hopefully helps us shape where we're going.
00:09:29.360 --> 00:09:36.559
So one thing that we've started to see in a lot of the phase three trials is combining therapies in a different way.
00:09:36.720 --> 00:09:42.960
And I do like to tell everyone that I combined Pick Ray, Kiscali, and Fastletx back before it was cool.
00:09:43.279 --> 00:09:49.840
But what is it that you're finding that patients are concerned about when you're talking about combining therapies?
00:09:50.639 --> 00:09:51.600
A hundred percent.
00:09:51.759 --> 00:09:53.200
You hit the nail on the head.
00:09:53.360 --> 00:10:03.360
We believe that if we combine therapies, this could be more efficacious because if you're hitting various targets, especially after CDK 4.6 inhibitors, what happens?
00:10:03.519 --> 00:10:08.480
What causes these tumors to develop resistance to the drugs that they're on?
00:10:08.639 --> 00:10:10.159
And this can happen early.
00:10:10.399 --> 00:10:11.279
This can happen later.
00:10:11.440 --> 00:10:21.679
We know in the trials that led to the approval of CDK 4.6 inhibitors, patients on average time before their next progression on scans was about two years.
00:10:21.840 --> 00:10:25.120
So for each of these patients, their tumors are all very different.
00:10:25.360 --> 00:10:36.000
A patient whose tumors progressed within less than two years, it's a very different disease than a patient who was on a CDK4-6 inhibitor for five plus years.
00:10:36.080 --> 00:10:37.360
And we have those patients.
00:10:37.440 --> 00:10:41.440
And so all of this helps us inform what we do next.
00:10:41.600 --> 00:10:48.320
And so to your point, Abigail, there's been a lot of push that, okay, if we combine therapies, if we hit various targets.
00:10:48.399 --> 00:11:00.799
And I can talk about a trial that was recently presented that looked at a triplet therapy that combined three very active agents together, but that came with efficacy, but it also came with toxicity.
00:11:00.879 --> 00:11:09.120
And so that's really where we have to think about okay, it's great to combine things, but where are we gonna get the biggest bang for our buck?
00:11:09.200 --> 00:11:15.279
Where are we gonna be able to truly add value to prolonging progression-free survival?
00:11:15.519 --> 00:11:26.240
But actually realistically having our patients be able to stay on these drugs and have some sort of quality of life and try to work towards better quality of life for our patients.
00:11:26.320 --> 00:11:30.559
So combinations are great, but I think that we have to look at each one very critically.
00:11:30.879 --> 00:11:40.960
So were you referring to the innovalisb trial that was presented last year at San Antonio as breaking news and again this year?
00:11:41.120 --> 00:11:43.840
And this is a very interesting first line treatment.
00:11:43.919 --> 00:11:45.679
Maybe we should talk a little bit about that.
00:11:46.000 --> 00:11:47.360
Yeah, absolutely, Victoria.
00:11:47.440 --> 00:11:48.799
So yeah, you're absolutely right.
00:11:49.039 --> 00:11:53.600
It was the Inovo 120 trial, and that actually was really exciting.
00:11:53.840 --> 00:12:13.440
Basically, there was a press release for positive results for the trial, and we were all in San Antonio, and everyone on the planning committee had worked together in a very speedy fashion to be able to present that while everybody was gathered at the San Antonio conference, and then there's been updated results since then, which has been awesome.
00:12:13.600 --> 00:12:18.639
And then there also was a trial called the Victoria One trial that also looked at a triplet.
00:12:18.799 --> 00:12:25.120
But for Inavo, that was looking at our patients who we believe are the patients that have the highest risk tumors.
00:12:25.279 --> 00:12:27.519
I don't ever really like to say highest risk patients.
00:12:27.600 --> 00:12:30.799
It's their tumors, it's their tumors that have the highest risk.
00:12:30.960 --> 00:12:39.600
But really, these are patients who were on endocrine therapy or had recently completed endocrine therapy and they developed metastatic disease.
00:12:39.919 --> 00:12:44.559
In the adjuvant setting, we're talking about the adjuvant setting early stage breast scans.
00:12:44.879 --> 00:12:46.159
You got it, exactly.
00:12:46.320 --> 00:12:58.480
And so these patients were getting their endocrine therapy, and either while they were on it or within 12 months of having finished it, they unfortunately developed metastatic disease or stage four disease.
00:12:58.639 --> 00:13:01.039
So you would know right there, that's pretty aggressive.
00:13:01.200 --> 00:13:12.240
That means that these patients were getting treatment that was theoretically going around their whole body to try to prevent cancer from coming back, and despite that, cancer still came back.
00:13:12.399 --> 00:13:17.279
So there's something about that tumor biology that's very aggressive, unfortunately.
00:13:17.440 --> 00:13:21.840
So what they did is they looked at patients who have the PIC3CA mutations.
00:13:22.080 --> 00:13:23.440
I alluded to that earlier.
00:13:23.600 --> 00:13:28.320
So that's one of the mutations that a patient can have that can drive tumor growth.
00:13:28.480 --> 00:13:36.000
And this can happen after treatment, but more commonly when tumors develop first, they have this mutation.
00:13:36.080 --> 00:13:38.480
It's what we call a truncal mutation.
00:13:38.639 --> 00:13:47.039
And really what that means is at the genesis of the tumor, when the tumor was born, this is more common for patients to either have this mutation or not.
00:13:47.279 --> 00:13:51.440
I believe it's about 40% of patients that can have this mutation.
00:13:51.679 --> 00:13:58.960
And so what they did is they identified these patients that have this mutation and they gave them three agents.
00:13:59.120 --> 00:14:01.360
And the new agent was in evolution.
00:14:01.679 --> 00:14:05.519
So it's a PI3K alpha isoform inhibitor.
00:14:05.600 --> 00:14:08.720
So it's very specific against this mutation.
00:14:08.960 --> 00:14:20.559
And then when combined with the Ibrands and with fulvestrant, it actually improved the amount of time the patients had before the next treatment that they needed.
00:14:20.720 --> 00:14:27.039
And then actually, we got some updated results this past year that it resulted in patients living longer.
00:14:27.279 --> 00:14:29.279
And so that's overall survival.
00:14:29.519 --> 00:14:35.600
In general, we end up needing to wait a long time with all of these new trials to get overall survival.
00:14:35.840 --> 00:14:46.320
So the fact that we have overall survival data on this group of patients already tells you right there that this is a very aggressive tumor group that we're treating.
00:14:46.559 --> 00:14:50.720
And so at this point, this is very much something that we're adopting in practice.
00:14:50.879 --> 00:15:03.679
And we really encourage every provider that is seeing patients to try to do profiling or mutational analysis up front so that we can see if this is a treatment option for those patients.
00:15:04.559 --> 00:15:12.399
But I will caveat that it's approved in a very specific fashion and it should be given the way the label is evaluating it.
00:15:12.480 --> 00:15:18.240
So, not for patients, for example, who developed de novo disease and they never had gotten endocrine therapy to begin with.
00:15:18.399 --> 00:15:19.759
It wasn't looked at in that fashion.
00:15:19.840 --> 00:15:23.679
There are trials that are looking at inovolisive in other ways.
00:15:23.919 --> 00:15:33.440
But really, this is how the trial was studied and this is how the drug was approved, just as you said, Victoria, as patients were getting endocrine therapy in the early stage setting.
00:15:33.840 --> 00:15:38.240
That's the medication, though, that there was a pretty high incidence of stomatitis, right?
00:15:38.320 --> 00:15:46.399
So controlled the hyperglycemia, not so much of the rash, but the stomatitis, I think, was pretty significant, a grade three.
00:15:46.720 --> 00:15:47.519
Yes, you're right.
00:15:47.679 --> 00:15:49.440
And hyperglycemia as well.
00:15:49.600 --> 00:15:58.559
And there's a lot more data that's coming out and anecdotal experience from folks that are using these drugs, and especially in the community.
00:15:58.799 --> 00:16:03.919
Because if you think about it, these patients who are on trial, they're fit enough to be able to go on trial.
00:16:04.080 --> 00:16:12.799
They're able to get to a center where there is a trial offered, and there's a number of factors that plays into a patient group that's on clinical trial.
00:16:12.960 --> 00:16:20.240
So then when you institute that into the community and widespread use, you can see slight differences there.
00:16:20.480 --> 00:16:21.759
Because there's a lot of different things.
00:16:21.919 --> 00:16:29.759
We have lots of patients who are faced with diabetes, especially in the United States, and it's important to think about that if that's a side effect that we're experiencing.
00:16:30.000 --> 00:16:36.080
Now, in the trial, they did have cutoffs for hemoglobin A1C, and that is important here.
00:16:36.240 --> 00:16:46.240
But really, to your point, Abigail, stomatitis, so mouth ulcers, being on top of that, and then hyperglycemia, and then also there was some rash there too.
00:16:47.679 --> 00:16:53.279
This regimen is tough, but at the same time, sometimes people think that this is the first line.
00:16:53.519 --> 00:17:02.720
So these people who come into the first line treatment are still pretty healthy overall for the most part.
00:17:03.200 --> 00:17:07.680
So if there were time to go aggressive, this would be it.
00:17:13.039 --> 00:17:16.000
So let's talk a little bit about Victoria, shall we?
00:17:16.160 --> 00:17:16.640
And you know.
00:17:16.880 --> 00:17:19.680
It warms my heart to talk about Victoria.
00:17:20.799 --> 00:17:28.400
I will say, I feel like in the field of breast cancer, we do come up with some pretty cool names and ones that are easier to remember.
00:17:28.559 --> 00:17:35.519
I think my colleagues who are practicing in other tumor groups will comment on that that we're quite creative with our names.
00:17:35.599 --> 00:17:38.079
So definitely love the Victoria trial.
00:17:38.160 --> 00:17:42.640
And I'll briefly step back to this is what we were talking about earlier with triplet therapies, right?
00:17:42.720 --> 00:17:53.839
So if we feel strongly that a triplet's going to work, and not only does it allow patients to have more time before they progress again, but it actually allows them to live longer.
00:17:54.000 --> 00:17:57.759
This is where we do our risk-benefit analysis and there's a trade-off there.
00:17:57.920 --> 00:18:14.720
But it's also so important to make sure that both our patients and all providers who are using these drugs feel empowered and educated on how to act ahead, how to try to prevent toxicities, how to counsel their patients on it, and how to think about these things, right?
00:18:14.799 --> 00:18:28.880
And then not just incorporating uh pharmaceutical type interventions, so lifestyle interventions that we should be able to talk about with our patients and other strategies that they can use at home because I think everybody is motivated to.
00:18:28.960 --> 00:18:30.720
We just have to be able to talk about it.
00:18:30.880 --> 00:18:32.720
And that's where we have to weigh things out.
00:18:32.880 --> 00:18:36.000
But Victoria, so this was a really exciting trial.
00:18:36.240 --> 00:18:41.839
It was presented first, as I mentioned, in Europe this past year, 2025.
00:18:42.160 --> 00:18:47.119
So this was evaluating a drug that we call getatolisin.
00:18:47.359 --> 00:18:50.480
Can we just say that the way that they develop names?
00:18:50.640 --> 00:18:53.599
These names are so hard to pronounce.
00:18:53.759 --> 00:18:55.599
I realize that it'll be the same.
00:18:55.759 --> 00:18:59.759
So alpella sib, sib, getolisib, right?
00:18:59.920 --> 00:19:06.559
We know that it's in that PI3 kinase pathway class, but they're still so hard to say.
00:19:06.799 --> 00:19:07.680
You're absolutely right.
00:19:07.759 --> 00:19:09.519
And there's so many more that are coming out.
00:19:09.680 --> 00:19:14.000
I think when Vab Degastret was first published, for example, that's another one.
00:19:14.319 --> 00:19:14.799
The mouthful.
00:19:15.119 --> 00:19:17.839
Everyone was like, how do we say this drug name?
00:19:18.559 --> 00:19:22.799
We definitely appreciate an easier way to be able to identify these drugs.
00:19:23.039 --> 00:19:31.279
But yeah, so Victoria was evaluating a novel drug called get a tolecid, and this is a PAM pathway inhibitor.
00:19:31.359 --> 00:19:32.319
So, what does that mean?
00:19:32.480 --> 00:19:46.799
So we do know that as I mentioned before, there's the PI3K pathway, and that's one pathway that tumors can utilize to enhance their tumor growth along with the mTOR pathway and AKT.
00:19:46.960 --> 00:19:48.880
So these things all work in sync.
00:19:48.960 --> 00:19:52.720
And so this drug is a PAM pathway inhibitor.
00:19:52.799 --> 00:19:54.880
So it hits the full pathway.
00:19:55.039 --> 00:19:57.759
Although I'll caution, it's an IV drug.
00:19:58.000 --> 00:20:07.200
So this is a trial that's looking at combining the getatolis of the IV drug with Ibrands and fulvestrant.
00:20:07.359 --> 00:20:12.880
So here you have an intra drug, you have an oral drug, and you have an IV drug.
00:20:13.039 --> 00:20:15.200
All right, so that's what's going on here, right?
00:20:15.440 --> 00:20:19.039
But actually, it's a very smartly designed study.
00:20:19.279 --> 00:20:20.880
They have two different studies.
00:20:21.119 --> 00:20:29.599
One was looking at a group of patients that do not have a PIC3CA mutation, and then those that did have a PIC3C mutation.
00:20:29.759 --> 00:20:35.839
And the results that were presented so far were the patients that do not have a PIC3CA mutation.
00:20:36.000 --> 00:20:39.920
And so within that, there were three cohorts of patients.
00:20:40.079 --> 00:20:46.960
There was one group of patients who received all three drugs, the getta tollacib, the Ibrands, and the fulvestrant.
00:20:47.119 --> 00:20:52.160
The second group received the getta tolacib and the fulvestrant.
00:20:52.319 --> 00:20:55.759
And then the last group received fulvestrant alone.
00:20:56.000 --> 00:21:02.400
And there's a lot of questions here because really there was a group of patients who received only one drug.
00:21:03.039 --> 00:21:05.599
And back then, that was standard of care.
00:21:05.839 --> 00:21:07.200
That's what we were doing for our patients.
00:21:07.279 --> 00:21:08.480
That's what we had available.
00:21:08.640 --> 00:21:18.079
And this is a problem that we're running into as we're getting readouts for clinical trials, is that what we were doing back then is not necessarily what we're doing now.
00:21:18.240 --> 00:21:34.400
This is something that, you know, as the paradigm of hormone-positive breast cancer and really all areas of breast cancer, as we're shifting our standard of care, the control arm or the arm that's getting one specific type of treatment, which at the time was the standard, ends up changing.
00:21:34.559 --> 00:21:41.440
What's nice about this trial is that they did allow for patients who progressed to then cross over or switch to the other arms.
00:21:41.599 --> 00:21:43.039
So that's a positive thing.
00:21:43.200 --> 00:21:48.960
The other thing to mention is that this trial, along with all the other trials that we've talked about, these are global trials.
00:21:49.039 --> 00:21:53.920
So they're looking across the world and they're looking at patients in various countries.
00:21:54.079 --> 00:21:58.960
And that's also really important because the standard is different in all of these countries.
00:21:59.119 --> 00:21:59.759
What's approved.
00:22:00.480 --> 00:22:07.680
What's not approved, what investigators and clinicians are able to get for their patients versus not be able to give.
00:22:07.839 --> 00:22:12.880
And all of these things impact the results of a clinical trial and how we think about it.
00:22:13.039 --> 00:22:24.000
But nonetheless, the triplet combination resulted in an improvement in the progression-free survival for these patients without a PIG 3CA mutation.
00:22:24.319 --> 00:22:36.640
The updated results from the San Antonio Breast Conference this year, I believe, showed, if I remember correctly, it was about 12.4 months compared to 1.9 months with the fulvestrin.
00:22:36.799 --> 00:22:38.319
And what does this tell us here?
00:22:38.640 --> 00:22:45.519
One, we know that single agent endocrine therapy, like fulvestrin alone, is not sufficient.
00:22:45.759 --> 00:22:47.119
We can't do this anymore.
00:22:47.359 --> 00:22:56.160
Our single agent endocrine therapies that are approved, which we touched on before, the CERDs, that's for a specific patient population.
00:22:56.400 --> 00:22:59.599
But beyond that, we know combinations work better.
00:22:59.680 --> 00:23:02.400
And what we need to do is find the right combination.
00:23:02.559 --> 00:23:07.359
The great data, a lot of questions on the IV use, how practical that is.
00:23:07.519 --> 00:23:10.559
Maybe it is practical for some patients, maybe it's not.
00:23:10.720 --> 00:23:13.920
And so that really has to be considered when we take all of this into account.
00:23:14.000 --> 00:23:15.759
But again, very exciting data.
00:23:15.920 --> 00:23:17.680
I think we're moving forward.
00:23:23.599 --> 00:23:33.920
Before we continue, here is some quick context on why the updated Victoria One results from ASCO 2026 are such a big deal.
00:23:34.240 --> 00:23:43.119
Get a Tolus works by shutting down the entire growth signaling pathway that PIC3CA mutant tumors rely on.
00:23:43.279 --> 00:23:46.640
Not just one part of it, but the whole chain.
00:23:46.880 --> 00:23:58.400
In the Victoria One trial, it was tested in patients whose cancer had already grown through a CDK4-6 inhibitor and who had a PIC3CA mutation driving their tumor.
00:23:58.960 --> 00:24:00.559
The numbers were impressive.
00:24:00.880 --> 00:24:07.440
Patients on the getadolisp triplet went nearly 11 months before their cancer progression.
00:24:07.680 --> 00:24:10.640
The doublet hit just over 11 months.
00:24:10.880 --> 00:24:17.920
Compare that to five and a half months with alpelicip plus fulvestrin, the current standard.
00:24:18.160 --> 00:24:24.319
Both combinations basically doubled the time patients had before needing their next treatment.
00:24:24.880 --> 00:24:27.279
And here is the other big win.
00:24:27.440 --> 00:24:31.200
Alpelicip has always been tough on blood sugar.
00:24:31.519 --> 00:24:43.519
Get a tellycip caused far fewer severe blood sugar spikes, which means patients may actually be able to stay on it longer, better results, and easier to tolerate.
00:24:43.680 --> 00:24:46.799
That's what has oncologists paying attention.
00:24:47.119 --> 00:25:00.079
I can just very briefly touch on there is an ongoing trial called the Elevate trial that's actually looking at several different combinations of medications and it's constantly reading out.
00:25:00.160 --> 00:25:05.519
So at San Antonio, there were two combinations that were shared with us that also looked promising.
00:25:05.599 --> 00:25:11.440
And so while that's a little bit earlier, it's a phase two trial, it also is giving us a lot of data on combinations.
00:25:11.519 --> 00:25:16.400
And as we go along, we're looking at safety and tolerability along with efficacy.
00:25:17.200 --> 00:25:18.720
So why don't we do that?
00:25:18.880 --> 00:25:23.920
Why don't we dive into this new exciting world of SERDs?
00:25:24.319 --> 00:25:28.559
Gamasestrin, alocestrin, gerodestrin.
00:25:29.039 --> 00:25:29.599
What else?
00:25:29.759 --> 00:25:30.160
Which one?
00:25:30.319 --> 00:25:31.599
Imlunestrin.
00:25:32.880 --> 00:25:33.680
You're so right.
00:25:33.839 --> 00:25:34.880
Pick your favorite one.
00:25:34.960 --> 00:25:35.680
There's so many.
00:25:35.759 --> 00:25:38.400
They're out there, many others that are under development.
00:25:38.559 --> 00:25:40.720
And Abigail touched on this before.
00:25:40.880 --> 00:25:42.079
What are CERDs?
00:25:42.480 --> 00:25:48.079
So, as she mentioned, just perfectly mentioned, these are selective estrogen receptor graders.
00:25:48.240 --> 00:25:51.279
And these are a novel form of endocrine therapy.
00:25:51.440 --> 00:26:04.960
So, unlike the previous generation of endocrine therapies, which either blocked the production of estrogen, or they, for example, competitively inhibited receptor activation, these SERDs directly degrade the receptor.
00:26:05.119 --> 00:26:14.400
And this type of mechanism, it allows SERDS to overcome one of the key resistance mechanisms that can develop to, for example, aromatase inhibitors.
00:26:14.480 --> 00:26:23.119
And that is what I briefly touched on before, which is an ESR1 mutation, in which the receptor is constituently activated.
00:26:23.200 --> 00:26:26.000
So it's constantly on, it's constantly running.
00:26:26.160 --> 00:26:31.440
And so if you can degrade that receptor effectively, that's one way to target this.
00:26:31.680 --> 00:26:47.279
We do know that these SERDs are still active in patients who don't necessarily have an ESR1 mutation, or that ESR1 mutations are driving the cancer or leading to the growth of tumors, but on their own, they're not sufficient.
00:26:47.359 --> 00:26:50.160
And this is again where the combination therapy comes in.
00:26:50.319 --> 00:27:10.799
But nonetheless, the SERDs are very exciting, and we have two that are out there in the metastatic setting that have been approved for those patients that have ESR1 mutations and multiple other SERDs that are being studied in combination with other targeted therapies like CDK4-6 inhibitors, which are all very exciting.
00:27:11.119 --> 00:27:22.079
There also was presented this year the use of cambasestrin, Victoria, you mentioned this, which was studied in the Serena 6 trial presented at ASCO this past year, 2025.
00:27:22.319 --> 00:27:24.960
This was a really novel type of clinical trial.
00:27:25.039 --> 00:27:45.279
So these are patients who were already on their first line of treatment, the aromatase inhibitor and CDK4-6 inhibitors, and they looked at what we call circulating tumor DNA, so fragments of DNA that was shed by tumors into the bloodstream to evaluate for ESR-1 mutations showing up in the blood.
00:27:45.440 --> 00:28:14.799
And they were looking to see, this trial was looking to see that if you switch the aromatase inhibitor to the CERD and keep the CDK4-6 inhibitor going, versus if you continue the aromatase inhibitor as those patients were receiving with the CDK4-6 inhibitor until the scans picked up progression, which is the way that we treat our patients most commonly right now, doesn't make a difference in how long patients have until their next progression.
00:28:15.039 --> 00:28:19.359
What we did find is that medium progression-free survival, it was prolonged.
00:28:19.440 --> 00:28:20.559
It certainly was.
00:28:20.799 --> 00:28:23.359
However, there's a lot of caveats here.
00:28:23.599 --> 00:28:31.440
We didn't really quite identify, at least not yet, that if we switch treatments, are patients really living longer?
00:28:31.599 --> 00:28:38.960
Or are we just moving our treatments earlier and using up some of our good treatments earlier than they need to be used up?
00:28:39.119 --> 00:28:41.119
And that still remains to be seen.
00:28:41.359 --> 00:28:47.279
I think CT DNA or circulating tumor DNA is very cool technology.
00:28:47.440 --> 00:28:48.640
I think we're getting there.
00:28:48.799 --> 00:28:52.000
I don't know that we're quite there, but we're getting there.
00:28:52.160 --> 00:29:05.759
I really believe in the next three to five years, we hopefully will be there in really detecting at a low level these mutations in the blood and then trying to figure out how exactly we act on them.
00:29:06.000 --> 00:29:08.960
And then really, it gets more complicated than that.
00:29:09.119 --> 00:29:14.559
Of all patients who have ESR1 mutations picked up in their blood, do all of them need to switch?
00:29:14.720 --> 00:29:16.240
Maybe only some of them need to switch.
00:29:16.400 --> 00:29:21.279
We have to try to hone in on really personalizing this type of strategy.
00:29:21.359 --> 00:29:22.240
It's a great strategy.
00:29:22.319 --> 00:29:29.680
It's really unique, it's really novel, but it may only be important for us to do this for some patients, maybe not all patients.
00:29:29.839 --> 00:29:33.920
And that's really where we need to go, and that's where I believe that we're headed.
00:29:34.240 --> 00:29:42.559
Sarah, you are at a wonderful institution who is very much looking at those biomarker testing, looking at CT DNA.
00:29:42.799 --> 00:29:50.160
And that's great for people who are in an academic setting or treated at one of these wonderful comprehensive cancer centers.
00:29:50.319 --> 00:30:02.079
But we know a large majority of people living with cancer are treated in a community setting, in a rural setting, often with an oncologist who may not specialize in breast cancer.
00:30:02.319 --> 00:30:04.720
And so we're talking about these great tests.
00:30:04.799 --> 00:30:07.440
You talked about biomarker testing early on.
00:30:07.599 --> 00:30:09.920
You talked about CT DNA testing.
00:30:10.160 --> 00:30:25.920
What is the language that patients can be using to ask their doctors for the testing that will give them these targets or give them more options for treatment for those people whose doctors may not be up on all the tests for all the different kinds of cancer?
00:30:26.079 --> 00:30:27.599
Because not everybody can do that.
00:30:27.839 --> 00:30:29.599
You're exactly right, they can't.
00:30:29.759 --> 00:30:34.880
So a lot of these providers in the community, they're seeing every type of cancer.
00:30:34.960 --> 00:30:41.920
And I'm so lucky that I get to specialize really in breast cancer, and then I also treat patients with gynecologic cancer.
00:30:42.079 --> 00:30:44.960
But a lot of providers they don't have that luxury.
00:30:45.119 --> 00:30:49.839
They're keeping up to date, as you mentioned, on so many different types of cancers.
00:30:50.000 --> 00:31:00.079
And they're, for example, walking down a hallway and they're seeing a patient that has a blood cancer, and then they're seeing a patient that has lung cancer, and they're seeing a patient that has a GI cancer and breast cancer.
00:31:00.160 --> 00:31:04.799
And while the field of breast cancer is moving fast, so are all these other tumors.
00:31:04.880 --> 00:31:07.920
And so, how do they truly keep track of all of this?
00:31:08.160 --> 00:31:18.319
Now at Sarah Canon, we are predominantly academic in the sense that we have investigators here who get the chance to do research and also see patients.
00:31:18.559 --> 00:31:22.720
The network is fully integrated within the community, which has been so awesome.
00:31:22.880 --> 00:31:30.480
So we've got sites that are all over the community and we work with local community doctors to try to enroll patients onto clinical trials.
00:31:30.559 --> 00:31:37.119
And through that, it's been great because we get to work with clinicians who treat all types of cancers.
00:31:37.279 --> 00:31:48.799
And if these providers are able to work with their patients who want to go on clinical trials and educate their patients on clinical trials, they get to use these drugs earlier than sometimes they're approved.
00:31:48.880 --> 00:31:51.200
And so then they feel more comfortable with using it.
00:31:51.359 --> 00:32:00.079
They're able to really teach their other colleagues who they work with on how to mitigate side effects or how to act ahead or how things were instituted.
00:32:00.640 --> 00:32:14.240
But for any patient who's interested in learning about clinical trials, there's so many patient advocacy groups that are out there that really partner with a lot of these institutions in trying to teach what's out there, what's available.
00:32:14.480 --> 00:32:18.720
If there's any message I could give to any patient about this, it's ask questions.
00:32:18.880 --> 00:32:19.839
Ask your doctors.
00:32:20.000 --> 00:32:23.599
You can always ask, what were the latest clinical trials that were presented?
00:32:23.839 --> 00:32:24.880
Could we look at it together?
00:32:25.039 --> 00:32:26.640
Could we explore what's out there?
00:32:26.799 --> 00:32:37.680
Or would you be willing to connect with any scientist that you know that maybe is a little bit more up to date on the breast cancer trials and maybe see if any of them would be options for me.
00:32:37.920 --> 00:32:46.000
But also, there's so many amazing resources that are geared to patient education because I just think our breast cancer patients, they're so savvy.
00:32:46.160 --> 00:32:48.480
They do their research, they know their stuff.
00:32:48.720 --> 00:32:49.839
Not everyone can.
00:32:50.000 --> 00:32:55.839
Some people don't have the chance to, some people don't have the means to, some people don't have the time to.
00:32:56.000 --> 00:33:00.559
And that's where really the partnership between a patient and a provider is so sacred.
00:33:00.720 --> 00:33:06.880
And I think that anyone I'm hoping is feeling encouraged and empowered to just ask their doctor questions.
00:33:07.039 --> 00:33:14.400
If they don't know exactly why they're getting what they're getting, what else they could be getting, don't be afraid to ask your doctor.
00:33:14.559 --> 00:33:17.359
That's why we're here, and that's ultimately what we're here to do.
00:33:17.440 --> 00:33:19.440
And so definitely encourage that.
00:33:21.519 --> 00:33:32.640
So we touched upon SERDs, and I think it's important to mention that even though CERDs are novel, we already have one CERD that we've been using for a very long time.
00:33:32.720 --> 00:33:35.759
It's pulvestrin or Fazilodex.
00:33:36.000 --> 00:33:42.640
So these are new novel oral SERDs, but they are not novel classic drugs.
00:33:47.359 --> 00:33:51.200
And speaking of gyrodestrin, or gerodestrin, you pick.
00:33:51.599 --> 00:33:56.799
We just got major news from ESCOTA 2026 that is worth a quick pause.
00:33:57.039 --> 00:34:00.960
Gerodestrin is a next generation oral hormone therapy.
00:34:01.119 --> 00:34:12.320
The idea being it could replace letrozole as the estrogen blocking partner alongside a CDK4-6 inhibitor, like polbocyclip, or Ibrands in the first-line setting.
00:34:12.559 --> 00:34:16.480
The phase three persevered trial put that to the test.
00:34:16.719 --> 00:34:22.719
Giridestrin plus polvocyclip versus the current standard of letrozole plus polvocyclip.
00:34:22.960 --> 00:34:24.960
Here is the honest read on the results.
00:34:25.119 --> 00:34:33.440
Patients on juridestrin went about 33 months before their cancer progressed, compared to 28 months on the standard arm.
00:34:33.679 --> 00:34:35.280
That's a five-month difference.
00:34:35.360 --> 00:34:39.840
And it's real, but it didn't cross the threshold for statistical significance.
00:34:40.079 --> 00:34:45.280
In clinical trial terms, that means we can definitely call it superior.
00:34:45.599 --> 00:34:47.920
Not a practice changer today.
00:34:48.159 --> 00:34:51.039
But here is the takeaway that often gets buried.
00:34:51.280 --> 00:34:57.360
Patients on both arms are now averaging nearly three years before needing to switch treatments.
00:34:57.519 --> 00:35:01.920
That's a remarkable benchmark for first-line metastatic breast cancer.
00:35:02.000 --> 00:35:05.519
And it tells us just how far this disease has come.
00:35:05.920 --> 00:35:08.159
Jodesterin isn't done.
00:35:08.480 --> 00:35:12.719
Longer follow-up and overall survival data are still to come.
00:35:13.039 --> 00:35:17.280
Okay, so let's talk about things other than CERDs.
00:35:17.360 --> 00:35:18.800
And there are many of those, right?
00:35:19.119 --> 00:35:22.719
There are CRANs and Protax, and what else is there?
00:35:23.280 --> 00:35:24.000
You got it.
00:35:24.159 --> 00:35:26.239
There are CRANs, there's Protax.
00:35:26.559 --> 00:35:27.039
CERMS.
00:35:27.199 --> 00:35:28.480
There's even a novel CERM.
00:35:28.639 --> 00:35:30.639
I've been on tamoxifen for 20 years.
00:35:30.800 --> 00:35:36.639
So this is interesting to see a new tamoxifen-like agent coming to market.
00:35:37.280 --> 00:35:37.760
Yep.
00:35:38.000 --> 00:35:40.800
This is what we call at this point our word salad.
00:35:40.880 --> 00:35:44.400
We have so many different types of novel endocrine therapies.
00:35:44.559 --> 00:35:51.119
Just as you said, we have a new generation of the selective estrogen receptor modulators.
00:35:56.159 --> 00:36:01.840
Before Sarah gives her own explanation, here is a quick breakdown of what a protuc actually is.
00:36:02.000 --> 00:36:06.960
Think of a protock like a seek and destroy mechanism for the estrogen receptor.
00:36:07.199 --> 00:36:13.519
Instead of just blocking it, the drug marks it for destruction using the cell's own internal disposal system.
00:36:13.760 --> 00:36:20.079
Once the receptor is tagged, it gets broken down, and then the drug gets recycled to do it again.
00:36:20.559 --> 00:36:26.719
That's what makes a dagostone different from a standard estrogen receptor blocker.
00:36:26.960 --> 00:36:43.440
On May 1st, 2025, the FDA approved a pedestrian for this exact indication, making it the third oral endocrine agent approved for ESR1 mutated metastatic breast cancer, joining LS estrant and immunestrin.
00:36:43.840 --> 00:36:54.239
And the tolerability profile is notably cleaned, low rates of nausea, minimal diarrhea, and a small, non-clinically significant QTC signals.
00:36:55.199 --> 00:37:01.840
A baseline EKG is recommended, but ongoing cardiac monitoring is not required.
00:37:02.159 --> 00:37:03.679
The protex, what are those?
00:37:03.760 --> 00:37:06.239
Those are proteolysis targeting chimera.
00:37:06.800 --> 00:37:07.840
Say it five times.
00:37:08.159 --> 00:37:09.599
Yep, yep, the protex.
00:37:09.679 --> 00:37:11.599
That's the BEP dagastriant that we talked about.
00:37:11.679 --> 00:37:16.079
That's one of the drugs that tries to more potently degrade the ER receptor.
00:37:16.159 --> 00:37:20.719
There's the CERANs, those are complete estrogen receptor antagonists.
00:37:20.800 --> 00:37:25.119
So what they do is they block multiple domains of the receptor to degrade it.
00:37:25.280 --> 00:37:28.320
So there's just so many exciting new drugs out there.
00:37:28.480 --> 00:37:35.840
But what we need to figure out is what we were chatting about earlier, which ones are the most effective for which patients and in what combination.
00:37:36.000 --> 00:37:38.800
And so that's really what's being studied now.
00:37:39.119 --> 00:37:39.519
All right.
00:37:39.679 --> 00:37:41.519
We have taken up a lot of your time.
00:37:41.679 --> 00:37:43.119
Well, we say goodbye.
00:37:43.360 --> 00:37:45.119
A difficult question for you.
00:37:45.280 --> 00:37:45.519
Yeah.
00:37:45.679 --> 00:37:48.480
So do you have an algorithm now?
00:37:48.719 --> 00:37:49.920
So what happens?
00:37:50.079 --> 00:37:52.320
Okay, you know what to do on the first line.
00:37:52.400 --> 00:37:53.360
Not quite, actually.
00:37:53.519 --> 00:37:54.559
There are options there.
00:37:54.800 --> 00:37:58.159
A lot of these drugs have not been approved yet.
00:37:58.239 --> 00:38:02.480
They're not FDA approved, they're only available in the clinical trial setting.
00:38:02.719 --> 00:38:13.280
But assuming they are going to be approved, what's the new algorithm for treating HR positive HER2 negative MBC population?
00:38:13.679 --> 00:38:21.760
In my mind, this is constantly evolving and it's evolving on a monthly, if not sometimes weekly basis.
00:38:22.000 --> 00:38:27.440
But just as you said, I really try to think about each patient in front of me individually.
00:38:27.599 --> 00:38:29.280
So there's a number of factors.
00:38:29.440 --> 00:38:37.119
Number one is doing what we mentioned, which is profiling their tumors, identifying which mutations do they have.
00:38:37.199 --> 00:38:52.639
Because even if they don't necessarily have a ESR1 mutation or a PIG3CA mutation, or we didn't touch on this, but a BRCA mutation, or the very rare mutations like NTREC fusions, for example, that opens up another treatment line.
00:38:52.719 --> 00:39:01.039
If they don't have one of those, it's still really important to know what mutations do they have, because that can tell you a little bit about their tumor.
00:39:01.280 --> 00:39:09.280
So doing that, also trying to look at how long was a patient on their first treatment, because that can give you a little bit of an idea.
00:39:09.440 --> 00:39:27.760
If they were on the first treatment for a long time, maybe they have endocrine sensitive disease, or the estrogen receptor is still playing an active role in the growth of a tumor versus a patient's tumor who's endocrine resistant, meaning their tumor found lots of other ways to grow around the estrogen receptor.
00:39:27.920 --> 00:39:29.199
So I think that's important.
00:39:29.440 --> 00:39:33.599
I think how a patient did on their first line treatment is important.
00:39:33.760 --> 00:39:35.920
What side effects did they experience?
00:39:36.079 --> 00:39:39.599
What are things to think about as we pick our next line of treatment?
00:39:40.000 --> 00:39:42.960
Also trying to think about what is the best thing for our patient.
00:39:43.119 --> 00:39:44.480
Do they live really far away?
00:39:44.639 --> 00:39:48.400
And trying to think about an oral regimen versus an IV regimen.
00:39:48.559 --> 00:39:52.719
And then what quality of life factors are important to our patient?
00:39:52.880 --> 00:40:01.599
If it's really important for that patient to be able to travel, then I wouldn't necessarily jump to an IV drug unless I felt like it was really needed for that patient.
00:40:01.679 --> 00:40:09.760
And then I would talk through that with that patient versus picking an oral drug, intramuscular drug, the fulvestrant, like you mentioned, depending on what they received in the first line.
00:40:09.840 --> 00:40:12.880
So there's just so many factors that go into it.
00:40:12.960 --> 00:40:17.199
But I think that the first thing is look at the patient in front of you.
00:40:17.360 --> 00:40:18.320
What did they receive?
00:40:18.480 --> 00:40:19.760
How long do they receive it for?
00:40:19.920 --> 00:40:21.679
What other conditions are they facing?
00:40:21.840 --> 00:40:23.360
What are their lifestyle factors?
00:40:23.599 --> 00:40:26.400
What is a priority for that patient at that time?
00:40:26.559 --> 00:40:29.920
Because that can change as well over a patient's lifespan.
00:40:30.079 --> 00:40:37.360
What certain life factors and what things are happening in their life outside of their cancer can certainly help you decide what you're doing next.
00:40:37.519 --> 00:40:39.840
And then of course, where are the sites of disease?
00:40:40.000 --> 00:40:42.159
Is this disease that's only in the bone?
00:40:42.320 --> 00:40:44.400
Is this disease that's spread to the liver?
00:40:44.559 --> 00:40:48.639
Is this involving the lungs, the bone, the liver involving all of these?
00:40:48.800 --> 00:40:50.000
Is the brain involved?
00:40:50.159 --> 00:40:52.400
These are all things that are really important to consider.
00:40:52.559 --> 00:40:55.599
I think also the subtype of breast cancer is important.
00:40:55.760 --> 00:40:58.400
We know our two most common is ductal and lobular.
00:40:58.480 --> 00:41:05.280
We didn't really go into the nuances there, but these are two different types of breast cancer, especially in the hormone-positive space.
00:41:05.360 --> 00:41:07.679
And so these are all things that play a role.
00:41:07.840 --> 00:41:13.280
If somebody has a lot of gastric disease, I would be hesitant to use something oral, for example.
00:41:13.440 --> 00:41:16.960
So there's just so many different factors that play into it.
00:41:17.199 --> 00:41:26.400
But starting first with overall survival data, we know that patients live longer with aromatase inhibitors and CDK4-6 inhibitors in the first line.
00:41:26.639 --> 00:41:39.519
Then after that, profiling our patients' tumors, understanding what mutations they have, and then taking into account all of the other factors to decide what is next, and then what is after that is really my approach.
00:41:40.400 --> 00:41:47.440
So basically, this is hard for you guys who specialize in breast cancer.
00:41:47.840 --> 00:41:51.519
What about the community general oncologists?
00:41:51.679 --> 00:41:54.639
How are they going to decide all of this?
00:41:54.880 --> 00:42:00.639
What is the role of AI, in your opinion, given this landscape right now?
00:42:01.039 --> 00:42:01.920
It's a great question.
00:42:02.079 --> 00:42:05.440
I think AI is being used in a lot of different ways.
00:42:05.599 --> 00:42:13.360
I think that providers are learning how to leverage AI, either to learn what the latest data is that's out there.
00:42:13.599 --> 00:42:16.719
We use AI for clinical trial matching sometimes.
00:42:16.880 --> 00:42:25.440
AI is being integrated more in pathologies when we look under the microscope and try to identify what type of cancer is there or what subtype of cancer is there.
00:42:25.599 --> 00:42:33.920
We can try to use AI for imaging, for modeling, and determining what could be there, and then also trying to integrate it with CT DNA monitoring.
00:42:34.079 --> 00:42:37.039
So I think AI is making its way into this.
00:42:37.119 --> 00:42:47.679
And the hope is that AI will help providers be more efficient at their jobs, and it will help because that relationship that I have with my patients is just so sacred.
00:42:47.840 --> 00:42:51.199
It's so special that I hope that never goes away.
00:42:51.440 --> 00:42:54.719
That's my favorite thing about my job, working with my patients.
00:42:54.960 --> 00:42:57.199
So I hope that is there to stay.
00:42:57.280 --> 00:43:02.159
But the other hope is that AI can be used to make our jobs easier.
00:43:02.320 --> 00:43:16.000
And this busy, evolving world that we're in, as there's so many competing efforts on our time and our attention, if we can use AI in the smartest way possible and responsibly, of course, making sure that AI is correct.
00:43:16.159 --> 00:43:21.760
That's what we're honing in on, is that it actually can help us enable us to do an even better job.
00:43:22.159 --> 00:43:28.480
To sum it all up, you're feeling optimistic about the future for this subtype.
00:43:28.800 --> 00:43:32.480
I certainly the most common subtype in breast cancer.
00:43:32.800 --> 00:43:37.679
The most common subtype, 70% of our patients having hormone-positive breast cancer.
00:43:37.920 --> 00:43:44.320
Feeling optimistic about all subtypes, but also in hormone-positive breast cancer, I think we've come a long way.
00:43:44.480 --> 00:43:46.239
I think we have a long way to go.
00:43:46.400 --> 00:43:55.280
I think we're trying to ask the right questions and we're actively trying to address them, whether that's in the lab, whether that's in clinical trials, and we all learn from each other.
00:43:55.440 --> 00:43:58.960
I learn from other investigators, we learn from our patients, learn from us.
00:43:59.039 --> 00:44:00.559
We're all one big community.
00:44:00.719 --> 00:44:07.840
And I really believe, I feel that together, the hope and prayer is that one day we will be rid of this.
00:44:08.000 --> 00:44:11.840
We will eradicate this and this will not be a problem for us anymore.
00:44:12.000 --> 00:44:13.760
I think we're moving closer there.
00:44:13.840 --> 00:44:20.159
I think we still humbly have a way to go, but at least if we're moving in the right direction, it gives us a lot of hope.
00:44:20.480 --> 00:44:23.119
That is such a wonderful way to end.
00:44:23.599 --> 00:44:27.280
Thank you so very much for being here.
00:44:27.440 --> 00:44:30.400
It was such a pleasure to have you with us.
00:44:30.800 --> 00:44:36.159
And I have learned something about you that you also treat gynecological cancer.
00:44:36.800 --> 00:44:41.760
So we need to have you back and talk about sex.
00:44:42.880 --> 00:44:44.400
I would be happy to join you again.
00:44:44.480 --> 00:44:45.039
Absolutely.
00:44:45.280 --> 00:44:46.079
Thank you so much.
00:44:46.159 --> 00:44:55.119
And we'll see you soon when we do the part two, when we talk about HERTU positive MBC.
00:44:55.519 --> 00:44:56.159
Take care.
00:44:56.480 --> 00:44:57.039
You got it.
00:44:57.119 --> 00:44:58.800
Thanks again for having me.
00:45:08.480 --> 00:45:10.800
That wraps up our discussion.
00:45:10.960 --> 00:45:12.320
Here's what we covered.
00:45:12.480 --> 00:45:17.920
The treatment landscape has evolved dramatically with oral SERDs now leading the charge.
00:45:18.239 --> 00:45:28.719
We discussed how CK46 inhibitors remain the first-line backbone and why ESR-1 mutations are a critical biomarker to track progression.
00:45:28.880 --> 00:45:44.000
We explored the new wave of endocrine agents, LSE and luminestrin, and lepiduchestrand, as well as next generation mechanisms like Protex and CERMS, and what distinguishes them from traditional estrogen receptor blockers.
00:45:44.159 --> 00:45:45.039
We heard from Dr.
00:45:45.199 --> 00:45:57.599
Sarah Pramgee about how she approaches treatment decisions in the real world, weighing tumor profiling, priotherapy sites of disease, and each patient's individual lifestyle and priorities.
00:45:57.840 --> 00:46:12.639
And we touched on the emerging role of AI in oncology, from clinical trial matching to pathology and imaging with the hope that technology can support and not replace the sacred patient-physician relationship.
00:46:13.840 --> 00:46:22.480
The bottom line we're in the period of rapid and meaningful progress for the most common subtype of breast cancer.
00:46:22.719 --> 00:46:31.440
The right questions are being asked, the trials are underway, and there is a real reason for optimism and a disclaimer.
00:46:31.760 --> 00:46:38.400
This podcast is intended for educational purposes only and does not constitute medical advice.
00:46:38.639 --> 00:46:45.039
The opinions expressed are those of the speakers and do not represent any institution or organization.
00:46:45.360 --> 00:46:52.079
Treatment decisions should always be made in consultation with a qualified healthcare provider.
00:46:52.480 --> 00:46:59.519
Thank you for being here, and we'll see you next time at Live from Stage Four.
00:46:59.679 --> 00:47:00.559
Goodbye.
