Live Chat: SERD Surge with Dr. Sherry Shen
Live from Stage 4 | Episode # 5 | 10/28/2025 | Live Chat
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Guests
Sherry Shen, MD
Dr. Sherry Shen is a medical oncologist and clinical investigator on the Breast Medicine Service at Memorial Sloan Kettering Cancer Center (MSK). She serves as co-director of the MSK Lobular Breast Cancer Program, one of the first dedicated clinical programs in the country for patients with invasive lobular carcinoma. This program provides multidisciplinary consultations, pathology review, and access to clinical trials tailored specifically to the needs of individuals with lobular breast cancer. Dr. Shen’s research centers on developing effective and personalized treatments for patients with hormone receptor-positive breast cancer, with a special focus on invasive lobular carcinoma. She leads clinical trials exploring the use of immunotherapy and novel endocrine therapies. Her work is supported by Conquer Cancer—the ASCO Foundation, the Terri Brodeur Breast Cancer Foundation, and Expedition Inspiration.
Rebecca A. Shatsky, MD
Board-certified breast medical oncologist and Professor of Clinical Medicine at the University of California San Diego (UCSD). She specializes in treating advanced breast cancer, with a particular focus on aggressive and rare subtypes
Dr. Shatsky focuses her clinical and research efforts on challenging and advanced breast cancer cases, driven by a passion to improve patient care. Her specialties include:
Specialization and research
Stage Four and High-Risk Early-Stage Breast Cancer: Treats patients with advanced disease, including significant lymph node involvement or inoperable tumors.
Lobular Breast Cancer (ILC): Dedicated to improving research and treatment for this subtype, which she notes is underrepresented despite accounting for 15% of all breast cancers.
Triple-Negative Breast Cancer (TNBC): Works extensively with aggressive subtypes, such as metaplastic breast cancer.
Leptomeningeal Disease and Brain Metastasis: Collaborates with neuro-oncology teams to treat these complications, which can affect both triple-negative and lobular breast cancer patients
Quick Summary
In this episode, the first in our ongoing “Live Chats” series — informal conversations with members of the medical community, advocates, and patients about what matters most to them and to us, hosts Victoria Goldberg and Dr. Ellen Landsberger are joined by Dr. Sherry Shen, a breast cancer medical oncologist at Memorial Sloan Kettering Cancer Center, for a clear, patient-centered conversation on the evolving role of SERDs (Selective Estrogen Receptor Degraders) in hormone receptor–positive metastatic breast cancer.
Dr. Shen explains the science behind SERDs, the importance of ESR1 mutations, and why oral SERDs are generating excitement. We review recent and ongoing trials—including evERA (giredestrant), SERENA-6 (camizestrant), and updates on FDA‑approved agents such as elacestrant and imlunestrant—while discussing regulatory and insurance hurdles, quality-of-life considerations, side-effect management, and how these drugs are shaping real-world treatment strategies and combination approaches.
Bonus clip: a preview from an upcoming episode with Rebecca Shatsky, MD, where she discusses the evERA trial and shares her enthusiasm for emerging combination strategies, including capivasertib paired with oral SERDs.
Whether you’re a patient, caregiver, or clinician, tune in for practical insights, expert perspectives, and a hopeful look at the future of breast cancer therapy.
Takeaways
SERDs Explained: SERDs (Selective Estrogen Receptor Degraders) are a class of drugs used to treat hormone receptor positive breast cancer, especially when resistance develops to standard hormone therapies (like aromatase inhibitors) due to ESR1 mutations.
ESR1 Mutations: These mutations allow the estrogen receptor to remain active without estrogen, leading to resistance against traditional hormone therapies. SERDs are particularly effective in patients with these mutations.
Oral SERDs vs. Fulvestrant: The original SERD, fulvestrant (Faslodex), is an injection with notable discomfort. Newer oral SERDs (Elacestrant, Imlunestrant, Camizestrant, Giredestrant) are easier to take and generally better tolerated.
FDA Approvals and Indications:
Elacestrant and Imlunestrant are FDA-approved for patients with ESR1 mutations.
Camizestrant and Giredestrant are in late-stage trials, with Giredestrant being studied in both ESR1 mutant and non-mutant populations.
Insurance coverage is closely tied to FDA label indications, limiting off-label use.
Comparing SERDs: The various oral SERDs have not been directly compared in head-to-head trials. Their effectiveness and side effect profiles are similar, with minor differences (e.g., Elacestrant more likely to cause nausea, Imlunestrant more likely to cause diarrhea, Camizestrant can cause bradycardia and photopsia).
Quality of Life: Oral SERDs generally offer better quality of life compared to injections, and having multiple options allows for better personalization based on patient tolerance and side effects.
Combination Therapies: Recent trials (SERENA-6, EMBER-3, evERA) show that combining SERDs with other targeted therapies (like CDK4/6 inhibitors or everolimus) can be more effective, especially for patients with more aggressive or resistant disease.
Early Detection and Switching: The SERENA-6 trial suggests that switching to a SERD upon detection of an ESR1 mutation (even before visible disease progression) can extend the time before further progression, supporting the value of early intervention.
Trial Design and Terminology: "Wild type" refers to patients without ESR1 mutations; "mutant" refers to those with the mutation. The proportion of patients with ESR1 mutations increases with more lines of hormone therapy.
Everolimus Side Effects: Everolimus, used in combination with SERDs, is known for causing mucositis, but preventive strategies (like steroid mouth rinses) are now standard to help manage this side effect.
Future Directions: The landscape is rapidly evolving, with more oral SERDs and combination strategies likely to become available, offering more options for personalized treatment after resistance to first-line therapies.
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Victoria: [00:02:08] So wonderful to have you with us. Thank you for being here. And before we start, why don't you just quickly introduce yourself to our listeners.
We know who you are, but let's have others
Sherry: learn about you. Sure. Thanks so much for having me. I'm really thrilled to be here. So my name is Sherry Shen. I'm a breast cancer medical oncologist at Memorial Sloan Kettering Cancer Center, and my research focuses on hormone receptor positive metastatic breast cancer, particularly lobular breast cancer.
So it's great to be here and to talk about these new drugs. Wonderful. Thank you so
Victoria: much again. The plan is today to talk about SERDs and as I was telling you and Ellen, just a few minutes ago, our original plan was to talk about Imlunestrant and how it compared to FDA approved Elacestrant, but hot off the press, just within the last couple of days at the ESMO 2025.
Symposium they [00:03:08] announced the results of the
evEra, is that the way we pronounce this? The evERA trial? Giredestrant in combination with everolimus. So we will shift gears and talk about that in addition to those others. Ellen, why don't we start with you?
Ellen: Sure. Let's start with the beginning and Dr. Shen, can you explain to us. What SERDs are, just in general what does SERD mean and why this is such a hot field.
Sherry: Absolutely. I think it's important to place that in the context and talk about ESR1 mutations as well. So for hormone receptor positive breast cancer, as we know, this essentially means that the tumor is driven by the female hormones, estrogen and progesterone. Those hormones act on the estrogen receptor and activate downstream transcription programs that tell the cell to grow and proliferate and be [00:04:08] aggressive essentially.
ESR1 mutations are mutations in a gene that result in a change in the confirmation of the estrogen receptor such that it doesn't depend on estrogen binding the estrogen receptor anymore, and it can just be active even without estrogen being present. So ESR1 mutations often arise as a mechanism of resistance to the most commonly used endocrine therapies we have, which are aromatase inhibitors.
So just to go through the different kinds of hormone therapies that we already have available I think of aromatase inhibitors as kind of an estrogen deprivation strategy, so taking away all the estrogen in the body. This is for our postmenopausal women or premenopausal women who are on ovarian suppression.
So the ovaries are not making much estrogen anymore, but we all have fat cells, which [00:05:08] are another source of estrogen. So aromatase inhibitors stop those fat cells from producing estrogen and thus deplete the estrogen in the body and don't let the estrogen receptor do its effects essentially. As I mentioned though, there are mutations like the ESR1 mutation that can develop that let the estrogen receptor not depend on estrogen anymore.
So this is where the SERDs come in, the selective estrogen receptor degraders. So what SERDs do is that they also bind the estrogen receptor. They induce a confirmational change such that it can't do its actions and as a result gets targeted for degradation or destruction within the cell. That's why it's called an estrogen receptor degrader.
So the original SERD, that we've been using for a long time is called fulvestrant, also known as Faslodex injection. I think probably many of you know from experience, it's a monthly injection. It can be [00:06:08] painful to get, it's an intramuscular injection. So there was a lot of interest in developing an oral version that people could take by mouth and not be beholden to monthly clinic visits and these painful injections.
So the oral SERDs are kind of the next generation of SERDs that are designed to be more powerful, have fewer side effects, and be easier to use. Okay.
Ellen: Okay, so I think what you're saying is that the first line of treatment is to use the aromatase inhibitor for, the majority of patients.
Right. And, and then if an ESR1 mutation develops and there's changes in the cell line and there's progression that these oral SERDs could be the next step. Yeah. Are they available to people who don't have the ESR1 mutation?
Sherry: That's a great question. So, it seems [00:07:08] like in the presence of ESR1 mutations, this is really where the Oral SERDs work very well, and they work less well in those without ESR1 mutations.
We know that people who have ESR1 mutations, it's generally a signal that the tumor is very dependent and addicted to the estrogen pathway. So this is where the Oral SERDs seem to have their most power, essentially. So Elacestrant, which was the first oral SERD that was approved, is available only for those with ESR1 mutations.
Imlunestrant similarly is approved for ESR1 mutations. Those are the two FDA approved Oral SERDs, but we've now seen Phase 3 data for two additional oral SERDs. One is Camizestrant, which came from the SERENA-6 trial. And then the other is Giredestrant, which we are now hearing about from the evERA trial as well. [00:08:08] So there's gonna soon be four Oral SERDs available thus far with Elacestrant and Imlunestrant.
These are FDA approved only for ESR1 mutations, Camizestrant Serena six was studied in the context of ESR1 mutations. So people had to be on their first line aromatase inhibitor and a CDK4/6 inhibitor and develop an ESR1 mutation in order to qualify for entry to the study. And then Giredestrant they studied in patients with and without ESR1 mutation.
So that one, we'll have to see eventually what the FDA approves.
Ellen: Okay. And I believe Camizestrant, they're studying in the people who have early stage disease Yes. And then presumably we'll see with those patients if it works with people who don't have the ESR mutation as well.
Sherry: Exactly. So Camizestrant and Imlunestrant also being studied in the early stage setting as well. Okay, great.
Victoria: But what I wanted to [00:09:08] ask you, and this is actually, I have a list of questions, but this was not on my list So all of these, as you just said, Elacestrant, Imlunestrant were approved for ESR1 mutated cancer.
But we had talked about the fact that Faslodex, which is a non-oral SERD, is a very painful monthly shot that people hate. The results of these trials showed that comparing to Faslodex non-ESR1-mutant cancers behaved no better and no worse, right? But the fact, the fact is. That for the quality of life of everyone.
Yeah. There is no comparison in what's no better and no worse. Faslodex is worse. So as a clinician, are you able to prescribe an oral SERD to a patient instead of Faslodex if they not ESR1 mutant ?
Sherry: Sounds a [00:10:08] great point. And you know, I think that kind of gets more to a root cause of how we're even approving these drugs, right?
We're so focused on effectiveness and comparing to this current standard of care, where I think there should be a lot of focus on quality of life as well, which is really important and side effects. And if the side effect profile or toxicity is better than the current standard of care as well.
So I think you raise a really good point. We know these oral SERDs are very well tolerated. We know, for example, from the SERENA-6 study that patients who switched to Camizestrant had better quality of life than those who didn't, although that was compared to aromatase inhibitors and not to Faslodex injections.
So I think you bring up a good point. It's not so much for us though, about whether we can prescribe it as much as it is about whether insurers will cover it. That usually falls pretty closely along the lines of the FDA approval. So insurers typically will not [00:11:08] cover medications that aren't per the FDA label indication, which means they typically will not provide coverage for giving these drugs to patients without SR one mutations as of right now.
Victoria: Right. You could potentially prescribe if somebody came to you and said, I don't have ESR1 mutated cancer, and I just hate Faslodex. I can't stand it and I'm ready to pay for yeah. I'm so rich. I'm ready to pay for my oral SERD
Could you potentially prescribe it?
Sherry: Yeah. That would be an off-label use. Off-label. Yeah. Yeah.
Victoria: Okay
so why don't we talk then about four different oral SERDs. And so the question comes up Do we really need so many of them?
Sherry: It's a great question. First of all, they're hard to compare to each other, I'll say, at least for effectiveness, because that's not what the trials were designed to do.
They were all [00:12:08] designed to be compared to the standard of care. Typically Faslodex, so I can't say for sure that one is so much more effective than the other. We don't necessarily have reason to believe that one would be so much more effective than the other. There are some differences in side effect profiles.
I think that makes a difference when selecting a drug for patient. But even then, there aren't so many differences there. But to get to your question, Victoria, I mean, we have three aromatase inhibitors available, right? We select one and start with one for patients, sometimes when they don't tolerate, we may switch to another, not expecting a huge difference.
It's the same mechanism of action, you know, same side effect profile, but sometimes patients just seem to tolerate one better than the other, and I think having several options is a good thing. In a similar case with the oral SERDs we may start with one that we think makes the most sense for that particular patient, but if for whatever reason they're having difficulty tolerating it
we could then theoretically switch to another, some [00:13:08] as we're talking about, are approved as a single agent, and may in the future be approved as combinations. So which combinations we can use will also make a difference and factor into how we select these drugs for our patient. But just at least to focus on the two currently, FDA approved drugs, Imlunestrant and Elacestrant.
These were studied in relatively similar settings, which is post one prior line of endocrine therapy. The Elacestrant trial required that everyone had prior CDK4/6 inhibitor. The Imlunestrant trial did not require that most patients did. About two thirds of patients did have a prior CDK4/6 inhibitor.
I say this because I think that influenced what the effectiveness of each drug looked like. Mm-hmm. So these drugs were each compared to Faslodex alone, and Elacestrant was significantly better. [00:14:08] Although significantly I say as in statistically significantly better. I think the actual difference in time that people got out of it was not that much more, it was certainly more and Imlunestrant relatively similarly, there was a statistically significant benefit over Faslodex injections, but it was overall modest, I think, in terms of numbers and number of months.
It's really hard to compare the drugs to each other 'cause they have not been studied in the same clinical trial. And I highlighted one difference in the way the clinical trials were conducted, which was the population of patients that was eligible for the trial. So while numerically it looked like Imlunestrant, there were patients got a longer time on it than the patients did in Elacestrant.
It's not really comparing apples to apples, it's kind of comparing apples to oranges because they're slightly different populations. So I think probably the drugs are pretty similar in the amount of time that they give. In other words, the [00:15:08] efficacy, the effectiveness of these drugs, the side effect profiles are relatively similar as well.
First of all, both drugs are associated with fatigue, and then Elacestrant seemed to have some more like upper gastrointestinal effects, nausea, vomiting. It still was associated with some diarrhea Imlunestrant, more so associated with diarrhea, less so with nausea and vomiting, but certainly these
gastrointestinal toxicities of both and Elacestrant can cause some abnormalities in the cholesterol levels, the lipid panel levels. So that is something we have to check with Elacestrant. That's one thing I would look at. You know, if someone has a history of high cholesterol that's been hard to control. Medications, for example, that might be one reason not to use Elacestrant.
Imlunestrasnt can still cause some slight abnormalities there but it seems like to a much lesser degree and doesn't warrant the monitoring that Elacestrant does. I think overall in summary, it's really hard to [00:16:08] tell in terms of the effectiveness difference between these two drugs. I think it's good to have two single agent options, very similar side effect profiles overall with just some very minor differences.
Victoria: Yeah, I mean, from menu one or menu two, you get to pick diarrhea or nausea. What do you pick? Uh, right. Well, why don't we switch gears and talk about ESMO and the evERA trial for Giredestrant. And it's an interesting oral SERD that a few years ago, an interview I did with Dr.
Stephanie said. It doesn't look like this drug is going anywhere, and all of a sudden it pops back into the picture. But now as a combination. Right. So one thing I want to mention that, the trial populations are very different sometimes, and this one seems to be more ESR1 mutant patients enriched than the other.
SERD trials, I think they said this one had [00:17:08] 55% ESR1 mutant population as opposed to general population of what 45%?
Sherry: We expect about 40%. Yeah. 40.
Victoria: Right. So you can expect better results from this trial right off the bat when as we know, SERDs do better with the mutant population.
Sherry: That's what we thought as well in this trial, which was that the effectiveness of the Giredestrant+Everolimus combination was more pronounced in patients with ESR1 mutation. So this is consistent with what, right. Kind of the story we've been seeing with the oral SERDs.
Victoria: One thing I wanted to ask you, again, this is just a little bit for our basic knowledge of trial designs and trial terminology. So when you see trial results on oral SERDs, and it's because of mutation, there are these two terms that keep popping up the wild type.
And mutant. Right. And I know I had a lot of [00:18:08] problems understanding what a wild type is, and I'm sure a lot of people as well. So maybe we can just quickly explain the difference.
Sherry: Yes, sure. So, patients whose tumors have ESR1 mutations, we often say that's ESR1 mutant versus wild type means non mutant, no ESR1 mutation.
Victoria: Why don't they just say no ESR1 mutation instead of making it wild type.
Sherry: Good question. Fewer words I guess. No, this comes from our scientific terms for genetics. So it's not specific to the trials, but yeah, I know. Makes it a lot less clear.
Ellen: I have two questions, just for clarification.
One, you were talking about 50% and 45%. Does that have to do with the amount of cells that have that mutation? What exactly were those percentages referring to?
Sherry: Yeah, that's a good point [00:19:08] for clarification. We were referring to the proportion of patients who have an ESR1 mutation, so we expect that with further lines of hormone therapies, the proportion of patients who have tumors with ESR1 mutations increases over time and approaches 45 to 50%.
I mean, even then there's heterogeneity within a patient themselves. They can have several different tumors. Some tumors can be more endocrine sensitive, and some can be more resistant than others. What we are really referring to is any detection of an ESR1 mutation on a liquid biopsy. On the Guardant test, for example.
And so if someone has an ESR1 mutation, regardless of which specific tumor that may have come from, for example if they have a mutation, they qualify for the oral SERDs currently Imlunestrant and Elacestrant. But you know, talking about SERENA-6 and now evERA as well, I do think that the [00:20:08] combination strategies are very important.
So we know from the EMERALD study, the one that led to the approval of Elacestrant that the patients who really benefit from a single agent oral SERD are those who seem to have relatively slow disease progression in general. There are patients who had a long time on their CDK4/6 inhibitor, and by long time, I mean at least 12 months, even better if it was 18 months or 24 months.
So those patients who had a long period of time on their first line drugs tended to do better on a second line oral SERD as a single agent, meaning by itself, but for many patients, that's not the case. And so I do think the combinations with targeted therapies are very important because it's not everyone who's gonna get benefit out of a single agent oral SERD.
When we looked at the whole trial population, not just [00:21:08] people who got that long period of time on the CDK4/6 inhibitors. The time on these oral SERDs was in the four to five month range. That's like two scans, you know? So I think we have a lot of work to do there that can be improved upon significantly with these combinations.
And we saw some sense of that from SERENA-6 with Camizestrant, where that was a switch strategy. It was looking for patients who were on their first line. AI and CDK4/6 inhibitor who developed an ESR1 mutation and then switched over, and that helped 'em get a lot longer of a time when they got Camizestrant plus continued on that same CDK4/6 inhibitor.
Going back to Imlunestrant, we saw from the EMBER-3 study that the combination of Imlunestrant and Abemaciclib, also known as Verzenio, was really powerful as well and better than either one of the single drugs alone. Now [00:22:08] that is not yet FDA approved. I think we have to see a little bit more data, including overall survival data, longer follow-up data there, but hopefully that will be approved because I think that combination strategy is a really good one.
And now we're seeing Giredestrant and everolimus as a combination strategy as well. So I do think for most patients, combination strategies make sense. For some patients who have more slow growing disease biology longer periods of times on each of these therapies and for patients who, suffer a lot of the toxicities of the combinations, that is where the single drug might make the most sense.
But I do think for a lot of patients, we're gonna be focusing on these combinations, and in the next few years we'll see a lot more data on various different combinations to come.
Victoria: SERENA-6 trial had a very interesting arm, and you actually talked about it . It was a switch trial yeah. So based on the CT DNA results, patients were switched to a different arm. [00:23:08] So this Was before the progression was actually visible on any, correct. Yeah. Any scans. So what is your opinion, first of all, do you think when the approval comes, it will come with the approval of this ctDNA test? Yeah. And the second question, what is your opinion? Is it more efficacious for a patient to switch earlier or to wait till the progression on the scans.
Sherry: Controversial Question. I know,
Victoria: I know. It's,
Sherry: I know it's, yeah. In the study, what they did was they screened patients every two to three months for development of an ESR1 mutation. And to be eligible to participate in the trial, there had to be no actual overt disease progression on a scan, so just the ESR1 mutation.
And then patients got randomized to either switching to Camizestrant, continuing on the same CDK4/6 inhibitor, versus just continuing on the same treatment alone and seeing when the actual [00:24:08] disease progression on the imaging scan happened. And the result was that there's a significantly longer time when you switched drugs.
Which I think makes sense . Interestingly, the other arm where they didn't switch, those patients actually still had an average of nine months before. Even change was detected on a scan, even though the ESR1 mutation was detectable. I do think scientifically it makes sense to target a resistant clone that we know is associated with resistance to aromatase inhibitors.
At a low detection level before it manifests as a new tumor in the liver, for example. So I think scientifically that makes a lot of sense. Also, what we saw was, I mentioned briefly there was a quality of life benefit in switching to Camizestrant. So I think those two, two things are huge considerations in thinking about the benefit of this drug, Camizestrant.
That being said, you know, I think the question is, well, can you catch up? [00:25:08] Basically, so in the patients who didn't switch, if they then had a scan showing that they progressed, can they just then get Camizestrant given that they have an ESR1 mutation, and it seems like the catch up period may be relatively similar, so possibly yes.
You could just catch up. But you know, if you think about it, that gave time for the tumors to grow to develop new spots, which can cause new symptoms in bones or cause liver test abnormalities. So that can be associated with more problems. So I do think probably an early switch strategy does make sense.
Now I'm not sure that we need to so closely monitor every single patient who goes on an AI and CDK4/6 inhibitor, because the average amount of time to developing or detecting an ESR1 mutation was at almost the two year mark. So I think especially when people are getting started on treatment, it's very overwhelming to need all these blood tests and constantly be looking for these mutations and thinking about switching
again, it's just a lot, and i think once patients get [00:26:08] past a certain point, maybe a year and a half, two years, then we should really be screening 'em. 'cause that's where we know the ESR1 mutations tend to develop and then employ this switch strategy.
Ellen: Dr. Shen, when the FDA approves of one of these new drugs, and if the drug's being used in a combination trial, is it the drug itself that gets approved or does the combination get approved?
In other words, can , once the drug is approved, yes. I understand the difference between off-label and whatever is it counted as off-label if you use it with a different additional drug?
Sherry: That's a good question the FDA will often approve it for example with Imlunestrant/Elacestrant as a single agent as it has been.
And then it may also approve the combination use. So specifically that combination. That being said, once the combination has been approved, I think it's a lot easier to dispense the drug and prescribe the drug even in slightly different combinations, based [00:27:08] on other data that there may be, as long as there's safety data that are out there, we sometimes try slightly different combinations and see what insurers will approve.
Knowing that there's Phase 1 and Phase 2 data to support these other different combinations. So, for example, like I and colleagues have had Elacestrant approved in combinations before. That is, again, not technically per the label, it's approved as a single agent, but there are some data out there supporting combination use and the safety.
And if we strongly think that that's appropriate for any given patient, we can certainly try.
Ellen: Yeah. I also wanna say, I think what's interesting when you say that these drugs have similar side effect profiles. Yeah. Yeah. That's in the aggregate and individual patients will exhibit different side effects.
And so I think absolutely really helps. Having more options.
Sherry: Of course. I think so too. And just mentioning the similarities and differences. Giredestrant looks pretty similar to Elacestrant and Imlunestrant in terms of the side effect profiles, primarily fatigue, [00:28:08] gastrointestinal, side effects. Camizestrant is a little bit unique among the four in that it can produce, um, bradycardia, which is a slow heart rate.
So it does warrant some EKG monitoring and this other side effect called photopsia, which is like a visual disturbance where there can be flashes of light for the eye. Yeah. That's not actually damaging to the eye, but it is a unique side effect. Both of those are unique. It seems to Camizestrant.
Victoria: We have time for one. Well, we don't, but, I'll pretend that we have time for one more question.
The last question I'm gonna ask you. Again, the evERA trial, the Giredestrant trial is actually a post-CKD4/6 inhibitor trial. So this is exciting. Yes. This is a new line of treatment for people after the CDK4/6 inhibitors don't work anymore.
I'm assuming, , what's your opinion on how it's going to change the landscape and the sequencing of treatments?
Sherry: So after CDK4/6 [00:29:08] inhibitors, we really use mutations to help guide what we do next. Mm-hmm. So for patients with PIK3CA, AKT, P10 alterations, we can give them capivasertib.
We formerly give quite a lot of Alpelisib for patients with PIK3CA mutations, but there are a subset of patients who have no mutations that are targetable. And those are the patients who we were trialing everolimus. Now we knew that everolimus, post CDK4/6 inhibitor was not that effective, which is that, it didn't produce nearly as long of a time as the first line CDK4/6 inhibitors, and the effectiveness was pretty limited.
And in patients in whom were using everolimus post a drug like Alpelisib or Capivasertib, it was even less. So, it was just a very short amount of time before patients developed disease progression. But that being said, I think that this is still a good drug, you know, and it's a good option for patients who don't have [00:30:08] PIK3CA/AKT/P10 mutations, which is the majority of patients.
And so I think it's really exciting to be able to now offer a better hormone therapy combination with everolimus and improve upon these treatments that we already knew we had, but make them even better with a stronger hormone therapy backbone. So I think this is really wonderful for our patients.
Victoria: Wonderful. So last, I promise I lied twice already, but the very, very last question. Sure. Just to let people know, a everolimus has always had a bad rep, because people were saying it comes with mucositis and Yeah. Yeah. It's horrible for those who've had it. It's a horrible side effect.
Mm-hmm. So. We have found ways to help people deal with it, right?
Sherry: Absolutely. Absolutely. It should be standard for patients to get the steroid mouth rinses in a preventative way when starting with [00:31:08] everolimus. So I mean, I agree. It's a horrible side effect. It's painful, I see my patients suffer or historically with this, but now I think with, newer, even clinical trials directed at
improving the side effects of everolimus, we now know pretty well how to control and prevent these side effects. And so I think hopefully that will help it to have less of a.
Victoria: we are done. Thank you so much. I mean, I don't need to do any editing.
I'll just put it out. It was, it's great. Thank you so much for being here and I'm really looking forward to talking to you about lobular breast cancer because that's such a, I would love that. That is such an important topic and I don't think we've ever covered it. At least I don't remember ever covering it.
Sherry: So good to be here anytime. Thanks for having me.
Victoria: Well, you shouldn't say that because you know what will happen next. You'll be my go-to person for every trial. Uhoh. [00:32:08] Thank you.
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Trials Mentioned
evERA (NCT05306340)
This Phase III, randomized, open-label, multicenter study evaluates the efficacy and safety of giredestrant plus everolimus compared with the physician's choice of endocrine therapy plus everolimus in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have had previous treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) and endocrine therapy, either in the locally advanced/metastatic or the adjuvant setting.SERENA-6 (NCT04964934)
A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (camizestrant) + CDK4/6 Inhibitor vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole)+ CDK4/6 Inhibitor in HR+/HER2-MBC Patients With Detectable ESR1Mutation Without Disease Progression During 1L Treatment With Aromatase Inhibitor+ CDK4/6 Inhibitor- A ctDNA Guided Early Switch StudyEMERALD (NCT03778931)
Elacestrant Monotherapy vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer Following CDK4/6 Inhibitor Therapy: A Phase 3 Randomized, Open-label, Active-controlled, Multicenter TrialEMBER-3 (NCT04975308)
A Phase 3, Randomized, Open-Label Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Patients With Estrogen Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer Previously Treated With Endocrine TherapyELEVATE (NCT05563220)
A phase 1b/2 open-label umbrella trial designed to evaluate the combination of elacestrant with alpelisib, everolimus, palbociclib, abemaciclib, or ribociclib.
