Newsflash: Updates from the 2025 ASCO Annual Meeting

LBBC welcomes Nan Chen, MD to share the most recent breast cancer findings from the 2025 ASCO Annual Meeting.  Join us to learn the latest medical breast cancer research presented at this year’s ASCO Annual Meeting and how this news may impact you. Attendees had the opportunity to ask Dr. Chen their questions during this free webinar.

Transcript

Caroline Koffke, RN, BSN, OCN [00:00:08]:

I am so, so honored and so excited to introduce you to tonight’s speaker, Dr. Nan Chen.

Dr. Chen is a board-certified hematologist-oncologist who specializes in comprehensive breast cancer care. And on a very personal note, she is a dear friend of mine as well as an outstanding researcher at the University of Chicago where she actively sees patients of all subtypes and all stages of breast cancer and does such so with such kindness, such compassion, and so much knowledge. We are just truly so thankful to have her here tonight, and especially someone as skilled as she is, to explain some of these very complex trials to us.

Nan Chen, MD [00:00:49]:

We’re going to be discussing updates from ASCO 2025, which was just last week, a couple miles down the road from where I am. It was a really exciting year for breast cancer. A lot of really exciting studies were presented. The studies that I’m going to talk to you guys about today are really the ones that I think are probably the most impactful and the ones that are probably closest to making it into the clinic. I could probably talk about a million other studies, but we’d be here until tomorrow morning.

To give us an overview of what we’re going to talk about today, I’m going to give a very brief introduction to clinical trials as a general refresher, and then we’re going to dive right into ASCO updates. We’re going to talk about all three subtypes of breast cancer. Most of these studies are in metastatic disease, but there’s one for early stage. We’re going to go through all of them, and at the end I’m going to talk for just a couple minutes about whether a clinical trial’s right for me, the things that a patient should consider when they’re making this decision with their oncologist.

The Food and Drug Administration is responsible for regulating all prescription medications in the United States. So all drugs that are used today outside of clinical trials have gone through an approval process. Before a drug is approved, it has to go through clinical trials.

Clinical trials can be categorized in many, many different ways, but one of the ways I think is the most convenient to think about is that they’re done in phases. It generally goes from phase I to III. Then after a drug is approved, they still do a lot of phase IV testing, which looks at how it works in a real-world population.

Phase I studies are usually the first types of studies that we have with a drug. These are focused on the safety because obviously we don’t want to give anything that’s unsafe to our patients. And they also look for the right dose to give patients. Usually this is done in anywhere from 15 to 50 patients.

If this study is successful, then we’ll move on to what’s called a phase II study. This is looking at how effective this drug is and at a larger portion of patients looking at its side effects. Usually these studies have somewhere around a hundred patients.

The studies that I’m going to be presenting today are larger studies and are primarily what we call phase III studies. These phase III studies compare the new treatment to the existing treatment that we have, because we want to make sure that what we’re trying to do is better than what we already have. These studies include large numbers of women, sometimes in the hundreds, some studies are even in the thousands. If a phase III study is effective, then the drug will get what we call FDA approval, which means that then we can use it across all women with breast cancer in the United States.

There are a few settings in which we will do breast cancer clinical trials. One area we’ll do that in is early-stage breast cancer before surgery. The goals of clinical trials here are to increase the likelihood that we can significantly reduce or even eradicate all cancer cells before surgery. We certainly want to find treatments that have less toxicity and side effects. We also want to find treatments that work in patients where some of our traditional usual treatments have not been effective.

Some of you may know that many women will receive a treatment after their surgery as well. Depending on a patient’s response at surgery, we may want to give them more medicine or less medicine afterwards. So goals of clinical trials in this arena would include drugs that we hope can decrease a patient’s risk of a cancer returning and specifically to match the appropriate level of treatment with the patient risk to reduce recurrence but not give patients really aggressive treatments if they don’t need it.
In metastatic breast cancer, there is a lot of active clinical research in this area, and this is where we’re going to be spending the most of our time talking. We want to find treatments that have less toxicity and side effects. We want to find treatments that are more effective than our current drugs and of course can extend to patient’s life and improve their quality of life. And then lastly, we also want to understand how do we use our existing therapies in sequence relative to each other for maximal benefit. That’s actually a theme that we’ll be talking about in some of our trials today.

Nan Chen, MD [00:05:04]:

Jumping straight into ASCO 2025, the first study we’ll be discussing is what’s called SERENA-6, and this is a study for HR [hormone receptor]-positive, HER2-negative disease.

The SERENA-6 study evaluated the combination of camizestrant plus a CDK 4/6 inhibitor. These are drugs, such as palbociclib [Ibrance], ribociclib [Kisqali], or abemaciclib [Verzenio], for the treatment of emergent ESR1 mutations during first-line endocrine-based therapy ahead of disease progression in patients with HR-positive, HER2-negative advanced breast cancer.

Many breast cancers have these estrogen or progesterone receptors. The estrogen receptor is made from the ESR1 gene. However, this gene can get mutated and that means that your estrogen receptor is always going to be on and it’s always going to be sending signals to the cell even if we use drugs to try to turn it off.
These mutations are pretty rare, less than 5% at the time of diagnosis, but when we treat patients with medicines such as aromatase inhibitors like letrozole [Femara] or anastrozole [Arimidex] in combination with CDK 4/6 inhibitors, the proportion of patients who develop these gets way higher.

Camizestrant is what’s called an oral SERD. It’s a selective estrogen receptor degrader. It basically blocks the estrogen receptor, and it’s a drug that is designed to inhibit both the mutated form of the estrogen flag as well as the normal form that isn’t mutated.

These ESR1 mutations can be detected in a patient’s blood. Some of you may have had a blood test from your oncologist that looked for different mutations, and you may have even gotten it more than once to track how it’s doing over time and how it’s changing. There was a previous study called the PADA-1 trial, which looked at, when you develop this mutation, changing your aromatase inhibitor to another drug called fulvestrant [Faslodex] to see if we can prevent the cancer from growing and try to control it for longer.

What the SERENA-6 study is evaluating is can we use this drug camizestrant to treat emerging ESR1, meaning we’re testing your blood every few months to see if you develop this change in your genes, ahead of disease progression, meaning ahead of the time where your cancer is seen to be growing on pictures, and whether us changing your normal aromatase inhibitor to camizestrant can actually extend our ability to use a CDK 4/6 inhibitor in your first-line therapy.

This was a very large study. This was a global, international study. They screened 3,300 patients with metastatic HR-positive, HER2-negative breast cancer who had been on their aromatase inhibitor with their CDK 4/6 for 6 months or longer. They checked these patients every few months through a blood test to see if they developed this ESR1 mutation. And in patients who had it detected, they then changed or kept going on their treatment.

Patients who had that ESR1 mutation in their blood, half of them just continue their usual therapy — either the anastrozole or letrozole plus their CDK 4/6 — or they changed it to camizestrant, which is this new drug that we’re evaluating in this study.
Ultimately about 150 patients in each group received either the camizestrant or continued on their AI drug. These groups are pretty evenly matched. Women were about the same age in both of these groups. The same proportion of women who were postmenopausal were in both of these groups. And then you can also see the rates of using the different CDK 4/6 inhibitors. Most of the patients in this study used palbociclib as their CDK 4/6, and then some patients used ribociclib and some patients used abemaciclib. Then this bottom one to point out is that there are different mutations that you can develop in your ESR1 gene, and there’s a variety of mutations that were included in patients in this study.

What they ultimately found was that patients who switched to the camizestrant and did not continue their aromatase inhibitor, their disease was controlled for longer. PFS stands for progression-free survival, and this is saying that your cancer was controlled for longer. More specifically, their cancer with camizestrant was controlled for about 16 months compared to patients who continued on their AI, their cancer was controlled for about 9 months. So the difference was about 7 months or so.

Nan Chen, MD [00:10:09]:

We are very concerned about patient’s quality of life, and we wanted to ensure that patient’s quality of life was not significantly affected by changing their therapies and by their cancer. Patients who were switched to camizestrant had an improved quality of life, and their time to deterioration, meaning the time that it took for their quality of life to be deteriorated, took longer. The median, or average, time to deterioration in patients who switched to camizestrant was about 23 months, but it was about 6.4 months in patients who continued on their aromatase inhibitor.

The second thing that they looked at was they wanted to see in patients who got another line of therapy after this, what patient survival looked like at that second line as well. And what they saw was that patients who switched to the camizestrant, even in their next line of therapy, their disease was controlled for a little bit longer than patients who stayed on the AI.

We talk a lot about toxicities, and toxicities are really important to discuss in this study as well. The most common toxicity that we see is neutropenia, or low white blood cell counts. This is likely not related as much to the camizestrant or the aromatase inhibitor. This is likely more related to the CDK 4/6 inhibitor that patients were on. But nonetheless, this was a really common side effect that we saw. CDK 4/6 inhibitors we use in the clinic a lot. We’ve been using it for about the last decade. This is also a really common side effect that we see in clinic. And those of you who are on a CDK 4/6, or have been, probably remember your doctor checking labs all the time and telling you about your white count and maybe even changing the dose because your white count was a little bit low.

Other common side effects were also related to blood counts such as anemia, or low red blood cells or hemoglobin, as well as leukopenia, which is another way to describe low white blood cell counts.

I want to point out an important side effect called photopsia, which is unique and specific to the camizestrant drug. Photopsia is this effect that you can develop in your eye where you can see flashes of light in the periphery of your eye. And this can happen especially in the dark. This is definitely a unique side effect. We haven’t really seen this in other breast cancer drugs, and about 20% of patients experienced this when they took camizestrant. And this was a really, really uncommon event in the AI arm.

Other side effects were relatively similar and can include things like arthralgias, or joint stiffness or muscle stiffness, fatigue, or tiredness. Some patients also develop dry eye, and nausea, which certainly can happen with many of our drugs, fortunately wasn’t super common with this combination.

The study concluded that when we switch an AI to camizestrant and continue the same CDK 4/6, this can improve the amount of time a cancer is controlled on this therapy. This benefit was consistent throughout subgroups, and the switching to camizestrant also delayed the time to deterioration in quality of life versus patients who continued the AI. The researchers thought that this has the potential to become a new treatment strategy in oncology to optimize first-line patient outcomes.

This was a really groundbreaking study that was done in order to evaluate how well camizestrant worked, but also to evaluate whether this strategy of testing patients for this ESR1 mutation before their disease itself actually changes on pictures is a good strategy that we should be using for our patients. Is this strategy really ready for prime time?

I think that it’s not necessarily the best option for everyone, and there’s a few reasons for that. One is that ultimately only about 16% of the patients had a positive test. You’re looking in a lot of patients and doing a lot of extra blood tests and stuff to look for not a huge number of patients. Secondly, about 43% of patients who had a positive test declined to participate in the study, suggesting that probably patients were concerned about the potential to continue the therapy that they were on. Furthermore, in this study, patients did not necessarily receive camizestrant in the next line, and only 10% of patients who didn’t receive camizestrant initially received a different oral SERD. An oral SERD called elacestrant, or Orserdu, is approved and can be given to everybody with an ESR1 mutation. But only 10% of the patients in the study in the non-camizestrant group actually received one later.

Then the next piece is that a larger portion of patients received chemotherapy in the camizestrant group as next line therapy compared to the group that continued on AI. And of course this is really important to us because we will try to delay chemotherapy as much as we can because we recognize that chemotherapy can certainly cause a deterioration in quality of life.

And then lastly, the most important question that we want to answer is, does this allow our patients to live longer, not just control their cancer for longer at this time, but does it allow them to live longer. And that question is still very much unanswered.

Overall, I think this was certainly a really, really important study. It could be a good idea for many patients, but it may not be the best option for everybody. But certainly lots of really interesting data from this study.

Caroline Koffke, RN, BSN, OCN [00:15:53]:

I’m going to hop on really quick because we have some great questions about camizestrant. Thank you so much for explaining that so well.

First question is a little bit general and may apply to all of these HR-positive trials that you’re talking about. For these trials or in your clinical practice, what percent of HR positivity are you using as your cutoff for considering someone HR positive?

Nan Chen, MD [00:16:20]:

That is a really good question, and in some ways I think maybe the clearest answer can be 10%. That’s a line in this sand. In reality, you have to ask yourself, do I really think that this is a cancer that’s being driven by estrogen stimulation. And I certainly think 10% is the clearest line in this sand, but if someone has 15% for example, it still means that I would probably try to use a CDK 4/6 inhibitor, but that if it doesn’t work very well, that wouldn’t surprise me and that this is probably a patient that might need to move on to something like chemotherapy or antibody-drug conjugates a little bit sooner.
Caroline Koffke, RN, BSN, OCN [00:17:00]:

OK, thank you. That’s really helpful. Next question is related to the ctDNA testing with camizestrant. I know you had mentioned that that happens every 3 months before progression, which is not how we would typically use that test. Someone asked, and this is actually more related to early stage, but maybe you can explain how this is being used differently with camizestrant than in early stage. They said that last year liquid biopsy ctDNA was discouraged because of the high false positive and false negative readings. Has that changed? So if you could share a little insight on that.

Nan Chen, MD [00:17:38]:

I really like the way that you framed it because I really do think we think about it differently in metastatic disease than we do in early-stage disease. So certainly for metastatic disease, for pretty much every single patient — especially with HR-positive, HER2-negative, but I would really argue for everyone — we should be doing ctDNA specifically to look for different mutations. Especially in HR-positive disease, this can actually affect what your doctor can give you. We know that there are certain medicines that we have, such as elacestrant or camizestrant, we know will work better for you if you have a specific mutation such as ESR1. And if we don’t know you have the mutation, then we’re not going to know whether or not to give that to you.

The other reason why it’s important to do ctDNA testing in the metastatic setting is because there are many, many clinical trials, which I’m not going to discuss today, but there are many clinical trials that specifically are looking for patients with a specific mutation. These are trials that not only include patients with breast cancer but may even include patients with lung cancer or colon cancer or other cancers but that all have a specific mutation that is making cancer behave in a certain way. And we might have a drug that blocks that mutation, in which case that clinical trial could be a good option for you. But if we don’t know that you have that mutation then then we don’t know that that exists.

For metastatic disease, I think it’s a good idea for everybody. Whether we do it every 2 to 3 months remains up in the air, and that data from the SERENA-6 study suggests that this could be a good strategy for some patients. I certainly don’t know if it’s a good idea for everybody, but it is certainly a conversation with your oncologist.
In the early-stage setting, it’s definitely a different story. The reason why is we are hoping that you don’t have any cancer leftover, whether it’s cancer in your breast that we can see, in your lymph nodes, or even cancer cells that we can detect in your blood. And so when we are doing ctDNA testing in the early-stage setting, our goal is really something different. One of our goals is to figure out do we have very tiny amounts of cancer swimming around in your body that we’re only able to see through this blood test and we can’t see with a picture.

One of the difficulties with using it commonly in the early-stage setting is that — unlike in the metastatic setting where if we see a result we can act on it, we know if we see this result we know what to do with it — that result-to-action relationship is much more muddy in the early-stage setting. And these tests can have false positives or false negatives, meaning that in some patients who don’t have any cancer cells for whatever reason the test turns positive or the opposite, which can be incredibly anxiety inducing for patients, for their families, for everybody. It’s very, very stressful.

It's definitely a very personal decision between a patient and their oncologist whether they want to check ctDNA in the early-stage setting. I do think our tests are getting better and so the risk of having that situation is definitely going lower, but the risk of that happening is certainly not zero. I still think the most important piece of this and what I always emphasize to my patients if they want me to order this test is I want you to understand what this test can and cannot do.

What we know about these tests in the early-stage setting is that if you are positive and consistently positive, meaning we see some evidence of cancer cells or cancer DNA floating around in your blood, it likely means you have a higher chance that the cancer is going to come back than if you’re persistently negative, meaning we never find any evidence of that. But unfortunately we haven’t really found any therapies yet that we know of that can change someone from a positive to a negative. We also don’t know what it means for someone to, for example, be negative then positive then negative again. There’s a lot of gray in there. So in my opinion if patients understand that and they still want to check and still want to know, these tests are available, but I do want to make it extra clear that there are definitely a lot of limitations to these tests. I think it’s important for patients to understand that.

Caroline Koffke, RN, BSN, OCN [00:21:49]:

That’s super helpful, and I think it’s really important what you highlighted. Have this conversation, see if the information that you would be able to get back from this test is something that’s of value to you, and then go from there.
A couple other really quick questions. Someone wanted just a little bit of clarification. They said being on an AI and a CDK 4/6 inhibitor can cause this ESR1 mutation based on the data that you were showing. If you could just explain that.

Nan Chen, MD [00:22:19]:

Actually it’s the AI specifically. The development of an ESR1 mutation is a well-known what’s called resistance mechanism, which means that unfortunately cancers are smart and sometimes they can outsmart some of our therapies. One of the ways that a cancer cell can become resistant to an AI is by developing this mutation where it no longer needs estrogen to work. AIs, as some of you may know, work by basically blocking the amount of estrogen that’s produced. You have this flag that’s sitting there but there’s no estrogen to combine to it, and so this flag isn’t active.

What the ESR1 mutation does is it basically makes the flag active even without estrogen. A drug like an AI, which blocks the production of estrogen, isn’t really going to help it. The reason why these other drugs, such as oral SERDs as well as another drug that I’ll be discussing next, work better is because they actually degrade or destroy the flag itself so that even if it doesn’t need estrogen, the flag is not active because we essentially destroy the flag there.

Caroline Koffke, RN, BSN, OCN [00:23:22]:

Very interesting. And just to clarify, patients in both groups were on two medications each, right? So you were either on your AI and your CDK 4/6 or the same CDK 4/6 and camizestrant.

Nan Chen, MD [00:23:37]:

Yeah. And just to clarify, AI plus CDK 4/6 is what we use all over this country as a standard treatment for women who have new HR-positive, HER2-negative advanced breast cancer. This study was evaluating in the portion of patients who developed this mutation, which again isn’t everybody but in that portion of patients who develop it, was switching to a different drug better than just keeping with the same two drugs you were on.

Caroline Koffke, RN, BSN, OCN [00:24:03]:

Great, thank you. Two more quick questions. Are you worried about the lead time bias in SERENA-6?

Nan Chen, MD [00:24:10]:

That is such an excellent question, and the short answer is yes. One of the critiques of this study was that for many of their patients, actually about half of their patients, on the first blood draw when they drew for the ESR1 patients were already positive. Meaning that they could have been positive earlier and we just didn’t know about it because we weren’t checking their blood. There’s a lot of thought about the timing. So the answer is yes, something to consider, and, again, why I think this is a conversation between a patient and their oncologist to decide whether they think the strategy is a good one for them.

Caroline Koffke, RN, BSN, OCN [00:24:50]:

Great, thank you. OK, last one and then I promise I will let you continue. How long until we think camizestrant might be in the clinic? And is it an oral medication?

Nan Chen, MD [00:25:02]:

It is an oral medication. It’s a once-a-day pill.

That’s a really good question. So camizestrant is not currently approved for use in breast cancer in this country. Certainly, with this data, camizestrant hopes to be approved and there are also upcoming studies looking at camizestrant in a couple other areas. So I think it’ll probably come in the next year or 2, but exactly how we use it and exactly when that will be remains to be determined.

Caroline Koffke, RN, BSN, OCN [00:25:29]:

Great. Thank you so much. I will let you keep going.

Nan Chen, MD [00:25:32]:

Absolutely. Those were really great questions. Excellent, excellent. So the next study I’m going to discuss is called the VERITAC-2 study. This is a study of something called vepdegestrant, it is a PROTAC ER degrader, versus fulvestrant in HR-positive, HER2-negative advanced breast cancer.

An ER PROTAC stands for a protein receptor destroyer, and it essentially destroys the estrogen receptor itself via this pathway inside the cell called ubiquitination and proteasomes. Vepdegestrant is a selective oral, so it’s also a pill, ER PROTAC that will degrade both an ESR1 mutated estrogen flag as well as a wild type — so non-mutated estrogen flag. They have already done a phase I and phase II study, which showed that vepdegestrant was well tolerated and worked pretty effectively in some patients.
Who was included in this study? Patients were over the age of 18, had advanced HR-positive, HER2-negative breast cancer. These are patients who did receive a CDK 4/6 and endocrine therapy earlier. They must have been on that endocrine therapy for at least 6 months, and they could not have received a prior SERD. So fulvestrant, elacestrant, they could not have received prior to this, and they also could not have received chemotherapy. This is what we call second line, meaning that their disease has already grown on a CDK 4/6 and now oncologists are looking for a next line of therapy for their patients.

Patients were randomized to either receive fulvestrant, which is an intramuscular SERD —some of you may have received this, it’s two shots every 28 days — or they receive vepdegestrant, which is a pill that patients take once every day.

Looking at the different patient groups, we see that they were pretty evenly matched. About 40% of patients in both of the groups had an ESR1 mutation. About 80% of patients in both groups had one line of therapy, and then a minority, about 20%, had two lines of therapy. Everyone had received a prior CDK 4/6 and most of those patients who had a prior CDK 4/6 got palbociclib, but a portion also got ribociclib as well as abemaciclib.

What we are looking at is a curve looking at progression-free survival, how long was a patient’s cancer controlled before they had to go on to another line of therapy. And what this showed was that in patients with an ESR1 mutation specifically, about 40% of the population, those who were getting fulvestrant, which is the standard of care, their disease was controlled for about 2 months, whereas patients who received vepdegestrant, their disease was controlled for about 5 months. So this was a positive study demonstrating that vepdegestrant in this specific setting was better than fulvestrant for these patients with an ESR1 mutation.

They also looked at how long the cancer was controlled in all patients, not just ESR1-mutated patients but patients even without an ESR1 mutation. And they saw that probably in an all-comer population, vepdegestrant was not any better than fulvestrant. So really the benefit of vepdegestrant over fulvestrant was limited to patients with an ESR1 mutation.

Of course, we want to talk about the safety and how well these drugs are tolerated.

Overall, very, very few patients, about 3% in the vepdegestrant group and 1% in the fulvestrant group, required a dose reduction or to discontinue treatment. Overall these patients, these drugs were very well tolerated, not that many patients needed to stop the drug or dose reduce the drug.

Nonetheless, probably the most common side effect they saw was fatigue, which I think many, many patients have experienced. About 27% of patients, or about a third of patients, who received vepdegestrant had fatigue, and about 16% of patients with fulvestrant also had fatigue.

The next most common side effect they noticed was an ALT or AST increase, which are elevations in the liver enzymes. Patients are very, very rarely noticing these symptoms. But this is the reason why your doctors are checking labs. This will also happen in about 14% of patients. Some patients notice a little bit of nausea, in some patients there was a little bit of decreased blood counts. The good news is that for grade 3 or 4, meaning these are the higher severity side effects, very, very few patients experienced higher severity side effects, meaning that there were some low grade or mild side effects but very few patients experienced severe side effects with vepdegestrant.

Nan Chen, MD [00:30:34]:

Ultimately vepdegestrant is the first PROTAC to be evaluated in a large phase III study.

Oral vepdegestrant demonstrated improvement in progression-free survival or how long we could keep cancer controlled in patients with ESR1-mutated, HR-positive, HER2-negative breast cancer. They’re still looking at overall survival, or how long patients are living with their cancer. So that data is not available yet. And that vepdegestrant was a pretty well-tolerated drug. There were very, very few adverse events that led to dose reduction or discontinuation and patients mostly had very mild side effects.

Caroline Koffke, RN, BSN, OCN [00:31:10]:

We have fewer questions about this one, if you can believe it. I know camizestrant was a big one.

One general question for these HR-positive trials: If someone is HR-positive but HER2-low, are they able to try these new drugs?

Nan Chen, MD [00:31:26]:

Yes. So HER2-low is a subcategory of HER2-negative. All HER2-low patients are HER2-negative, but not all HER2-negative patients are HER2-low.

Caroline Koffke, RN, BSN, OCN [00:31:39]:

Amazing. OK, another question: Can you explain the difference between vepdegestrant and fulvestrant?

Nan Chen, MD [00:31:46]:

Yeah, that’s a great question. So both of these drugs are drugs that target the estrogen flag that is present on the outside of cancer cells that have it, which is again about 60% to 70% of breast cancers. The way that fulvestrant works is it is a SERD, meaning it’s a selective estrogen receptor degrader; it essentially degrades the flag on the cell surface.

The PROTACs work a little bit differently. Instead of degrading it at the cell surface, it kind of sucks the flag into the cell and then the body degrades it in a different way using what’s called the ubiquitination proteasome pathway. It’s just a different way for that flag to be degraded. But ultimately the end goal of both of these medicines is to degrade the estrogen flag. They just do it in two different ways.

Caroline Koffke, RN, BSN, OCN [00:32:34]:

I really love the large words that you just threw at me on this Thursday evening.

Nan Chen, MD [00:32:38]:

I personally hate them but sometimes they have to be used.

Caroline Koffke, RN, BSN, OCN [00:32:41]:

I think you mentioned this, but PROTACs — this is a first-in-class PROTAC right?

Nan Chen, MD [00:32:46]:

Absolutely, this is the first time that we’ve developed a drug. There are other PROTACs that exist, but they are earlier in development. So this is the first PROTAC that we’re seeing in such a large study and to see how it performs. And you are absolutely correct, this is the first PROTAC in breast cancer that’s made it this far.

Caroline Koffke, RN, BSN, OCN [00:33:04]:

I’m going off script here, but I have a question. Why do we think that this worked better for ESR1 mutations than in the non-mutated group? Because I know the hope was that it would work for both.

Nan Chen, MD [00:33:18]:

Absolutely. And that’s a really good question. I think it has a lot to do with even the reason why the SERDs also work better for ESR1-mutated tumors than not. There’s a lot about the biology of how the estrogen signaling works and also how dependent on estrogen signaling the tumor cell is. It works better in a tumor cell that’s really, really dependent on the estrogen to keep it going.

This is a fancy way of saying I, I don’t think anyone knows 100%. I think that’s one leading thought of why that’s the case, and I think there are other drugs that do other things to the ER receptor. It remains to be seen if we can find a drug that works equally well in everybody.

Caroline Koffke, RN, BSN, OCN [00:34:04]:

Great, thank you. I know we do still have some residual questions from the camizestrant, and so if we have time at the end I’ll ask that. But I’m really excited to hear about TRADE so I’ll pass it back to you.

Nan Chen, MD [00:34:13]:

Great. So the TRADE study is a phase II trial to assess the tolerability of abemaciclib dose escalation in early-stage HR-positive, HER2-negative breast cancer.

Abemaciclib is one of the CDK 4/6 inhibitors. We’ve been using it in metastatic breast cancer since 2018 when it was approved, but more recently it was approved in the early-stage setting for high-risk HR-positive, HER2-negative breast cancer. For those of you who may know about abemaciclib or know someone who’s on it or have been on it themselves, you probably know that there’s a lot of diarrhea especially, but other GI side effects such as nausea or taste changes or just abdominal discomfort you can get from this drug. Especially this can happen very early. Managing this side effect has been really difficult for oncologists and patients alike, especially because this side effect can occur really quickly. It’s very discouraging for patients because this is a drug in the early-stage setting, where I’m telling patients you’re going to be on this drug for 2 years. I’ve had patients ask me, Am I going to be having diarrhea for 2 years? And the answer is I certainly hope not and I don’t want it to. And we need to find ways to make that not happen. But it’s very discouraging to have to take a drug that you think is going to cause you diarrhea for 2 years.

Ten percent of patients end up discontinuing abemaciclib by 12 weeks mostly because of these. And an even larger portion of patients, 27%, have to reduce their dose of abemaciclib because of these side effects. So figuring out how we can better utilize this drug and allow patients to stay on it is really important.

Abemaciclib, the usual dosing of this is 150 milligrams, twice a day. What the study did was that for patients who were going to go on adjuvant abemaciclib. So after their surgery they still had high risk HR-positive breast cancer and their oncologist recommended that, in addition to their endocrine therapy, they would take this drug abemaciclib. Instead of going straight to the 150 mg, twice a day. They first started patients on the 50 mg for 2 weeks, then they went up to 100 milligrams for 2 weeks, and then they finally went up to 150 mg.

Patients actually didn’t end up on the main dose for a month. This study included 90 patients. This was a study that was primarily done at a cancer center called Dana-Farber, which is in Boston, Massachusetts. Most of the patients were white, there were a few Asian patients and Black patients, and about half the patients were stage II disease and about half the patients were stage III disease.

What they saw was that 71% of patients were able to make it to the target dose of 150 mg, twice a day, that only about 13% of patients couldn’t maintain that full dose. And then about 9% of patients didn’t reach the full dose.

Most patients were able to meet the primary endpoint, which is to get into and maintain this target dose of 150 twice a day. So what this showed is that it allowed a greater number of patients than what we would expect to reach and maintain the 150 mg, twice-daily dosing than what was noted in the study that approved abemaciclib. And that even at 12 weeks, longer than being at the full dose, over 90% of patients were able to continue on therapy.

There were some patients who stayed on therapy at lower doses of either 50 mg or 100 mg, but they were able to stay on the drug without discontinuing it, which is still a win. And that this early dose-escalation strategy could be considered in some patients when we’re starting abemaciclib, with the hope that this allows more patients to stay on the drug for longer.

Caroline Koffke, RN, BSN, OCN [00:38:06]:

Interesting. This escalation scale seems like such a great practice change in order to make this more tolerable. There was a question that I’m interested in your opinion on. There’s been a lot of chatter that a dose reduction in abemaciclib, or Verzenio, is just as effective as taking the full dose. Can you shed a little bit of a light on that?

Nan Chen, MD [00:38:32]:

I’m going to say that it’s not even chatter. It’s absolutely true.

In the original study, which was the monarchE study, that evaluated abemaciclib in this patient population, they actually looked at patients who stayed on full-dose abemaciclib throughout the 2 years versus patients who had to reduce their dose down to 100 mg. And what they saw was that their outcomes, meaning how likely it was that their cancer came back, were not affected or not any different in patients who took the 150 mg or the 100 mg. We obviously want our patients to be on these drugs as long as long as we can, and to me that means we don’t have to push extremely hard to keep patients on the 150 mg. Some patients that may be the right dose for them, and that’s amazing. But in many patients that may not be the right dose. And 100 mg, in my experience, has worked out a lot better for most people.

Caroline Koffke, RN, BSN, OCN [00:39:20]:

Great, I remember that as well from working with you.

A question came in about what is considered high risk. I know this has been top of mind with the inclusion of CDK 4/6 in the early-stage setting. How do they define high risk for monarchE or for qualifying to get these CDK 4/6 in the early stage?

Nan Chen, MD [00:39:42]:

Specifically for abemaciclib, the way they defined high risk was that you must have had lymph nodes. So the cancer must have gone to the lymph nodes at least in your armpit or it could have gone to lymph nodes in other areas near your breast. In addition to that, you must have had another feature. One of those features could be that your cancer is over 5 centimeters. Another feature can be that your cancer is what we call high grade, and that’s something that’s on your pathology report, or another way to say it is grade 3.
And then another feature that it could be is that it could have something called a Ki-67, which is basically a marker of how quickly cells are dividing, and that number should be 20 or greater. Basically this set of criteria is what we use to define that.

There is another CDK 4/6 inhibitor called ribociclib that is also now approved in the early-stage setting. And that was based on the NATALEE study. The way that they defined high risk is much simpler, and it was basically anyone with stage II or stage III disease.

Caroline Koffke, RN, BSN, OCN [00:40:43]:

Just to clarify for everyone listening, grade 3 does not mean stage III.

Grade 3 is how your cells look under a microscope on your pathology report, and stage III is determined by size and spread.

Nan Chen, MD [00:40:56]:

Absolutely. Grade 3 is a feature of the cancer cells themselves, whereas stage III basically is a description of how much cancer you have or the volume.

Caroline Koffke, RN, BSN, OCN [00:41:04]:

Great, thank you.

TRADE obviously was done in the early-stage setting for Verzenio, or abemaciclib. Are there thoughts about using this dosing escalation for MBC as well?

Nan Chen, MD [00:41:18]:

That’s a really good question. Of course the TRADE study didn’t include patients with metastatic breast cancer. And I’m not aware of another study repeating this in the metastatic setting. That being said, I actually know many oncologists who outside of a clinical study utilize a dose escalation strategy on their own. And so they might start patients at 100 mg instead of 150 mg. And if you tolerate it really well, you can go up. But if you’re not tolerating it as well, maybe we stick to 100.

Caroline Koffke, RN, BSN, OCN [00:41:47]:

Great. And I always like to do a plug for patient-centered dosing or talking to your physician about how you’re feeling. You should be able to get out of bed in the morning, right? And if that’s not feeling right, then talk to your doctor because, as you’ve explained so beautifully, oftentimes these medications can be just as effective. So that’s really, really helpful.

Nan Chen, MD [00:42:08]:

There’s no way that I want a patient to be having diarrhea for 2 years. There’s no point in curing your cancer but ruining your life anyway. That’s absolutely not the goal. So please, please talk to your doctor. Be open and honest with them about what your side effects are so that you guys can make the best decisions together about what your care should look like.

Caroline Koffke, RN, BSN, OCN [00:42:26]:

OK, I’m going to let you keep moving so we can get into some HER2-positive and TNBC stuff. You all are absolutely crushing the question game. Thank you for all of these. I’m really hopeful that we can continue to weave them in and then do some at the end as well.

Nan Chen, MD [00:42:41]:

We’re going to move on and talk about HER2-positive disease.

The DESTINY-Breast09 study was a study looking at trastuzumab deruxtecan, or T-DXd or Enhertu — I know everyone loves the fact that all of our drugs have 13 different names — in combination with pertuzumab [Perjeta], and that was compared to either a taxane, so a drug like Paclitaxel or Taxotere, with trastuzumab [Herceptin] and pertuzumab for the first-line treatment of patients with HER2-positive advanced breast cancer.

Trastuzumab deruxtecan and pertuzumab are both drugs that act on HER2. The way that I like to think about HER2 is that it is a flag that is on the outside of many, many, many of our cells, and it is a normal flag to have. Most cells in our body have HER2.
HER2 is a normal signal for the cell to grow, and there are a couple ways by which HER2 can do that. One is that HER2 can bind to itself and that is called homodimerization, meaning a HER2 and a HER2 can meet and that’s a signal for the cell to say you need to grow. Another way that it can do that is by a HER2 binding to another one of the HER things such as a HER3, and that is called heterodimerization. So HER2 binds to a different HER molecule, HER2 binds to HER3. And this is also a signal to tell the cell to grow. Basically by combining T-DXd with pertuzumab, we prevent HER2 from binding to itself and we prevent HER2 from binding to HER3. And this ultimately inhibits cells from dividing and growing.

DESTINY-Breast09 was a study that evaluated patients with HER2-positive metastatic breast cancer. They did allow patients with brain metastases, and they did allow some endocrine therapy but no other prior systemic therapy for their metastatic breast cancer. They did allow patients who had early-stage HER2-positive disease who had their cancer came back as long as there was at least 6 months in between when their cancer came back and their therapy for their early-stage disease.

In this study, patients actually had the option of receiving three different therapies. One is chemotherapy with trastuzumab and pertuzumab, and this is our standard of care, meaning that if you went to your oncologist this was the treatment that they would offer you. It’s called THP. There were two other drugs that were studied. One was trastuzumab, deruxtecan with pertuzumab, and then one was trastuzumab deruxtecan with placebo.

In this data specifically, we’re only going to be talking about the trastuzumab deruxtecan-pertuzumab compared to the THP. The trastuzumab deruxtecan-placebo data has not been presented yet.

Nan Chen, MD [00:45:24]:

Looking at the different patient populations, we see this was also a global study including Asia, Europe, North America, and South America. Most patients were what we call HER2-positive 3+, meaning they were very, very HER2 positive. And then there were some patients who were HER2 2+, but still HER2 positive. About half the patients were HR-positive as well, so HR-positive, HER2-positive, and about half the patients were HR negative, HER2-positive.

The primary objective of the study was to evaluate how long patients were on study and how long patients’ cancer was controlled before they had to move on to something else. In the blue line we see the T-DXd, and in the gray line we see the chemotherapy plus the HP. We see that patients with the T-DXd and pertuzumab, their cancer was controlled for a longer period of time compared to patients who received the chemo with the HP. Specifically their cancer was controlled for about 41 months compared to about 27 months for patients who were getting the chemotherapy.

They also looked at whether or not the cancer responded, meaning whether the cancer actually decreased by over 30%, not just stayed stable and controlled, but actually decreased by over a third. What we see is that overall about 70% of patients, pretty similar in both groups, their cancer decreased at least 30%. However, there were a small portion of patients in which their cancer disappeared from their imaging. They had what we call a complete response, meaning when we took a picture of their cancer we could no longer see it. About 8.5% of patients experienced that with chemotherapy and Herceptin-Perjeta. However, about 15% of that, so a larger portion of patients had that happen to them if they got the T-DXd with pertuzumab.

Side effects are definitely very, very important in evaluating the study. Unlike some of the drugs we use for HR-positive disease, many of our HER2-positive drugs, especially Enhertu as well as chemotherapy, have a lot of side effects. You’ll see that some of the most common side effects that we saw were actually related to GI: nausea, diarrhea. Patients still had neutropenia, or low white blood cell count.

T-DXd is a drug that we’re already using in HER2 positive disease. We’re actually using it in HER2-low disease. So some of you who have even triple-negative breast cancer or HR-positive, HER2-low cancer may have also gotten T-DXd as well. What we’re really trying to figure out in the study is whether using it earlier, so instead of waiting until the cancer has already become resistant to chemotherapy and HP, whether using it earlier is better for patients.

A lot of the side effects that we see are side effects that are already known about T-DXd. So I would say that this side effect profile is not anything new than what we would’ve otherwise expected, both based on previous trials of T-DXd but also real-world experiences with these drugs. The other thing I want to point out is that interstitial lung disease, which is a really important side effect of trastuzumab deruxtecan was seen in the study as well, and unfortunately three patients passed away because of the interstitial lung disease.

Interstitial lung disease, or ILD, is basically a condition in which the drug stimulates the HER2 and it causes an inflammatory response in your lungs that can lead to scarring. Some of the symptoms of ILD are things like cough or shortness of breath. I always tell my patients that I’m starting them on this drug, please, please let me know if you develop a cough or shortness of breath or you notice that you are unable to walk as long of a distance without becoming short of breath. It’s really important to pay attention to. And that’s because unfortunately this happens in about 7% to 8% of patients and that unfortunately patients do die from this. That was seen in the study as well. But this is not different than what we’ve seen in previous studies with T-DXd.

What they saw was that T-DXd in combination with pertuzumab did demonstrate that patients were able to have their cancer controlled for longer as compared to chemotherapy with Herceptin and pertuzumab. And that the average amount of time that someone had their cancer controlled was almost 41 months with this therapy, which is over 3 years. And that they had a complete response in 15% of their patients.

They’re also looking at overall survival data. That is not yet mature but it’s favoring the T-DXd as well. And then the safety data with these drugs is consistent with what we already know.

Caroline Koffke, RN, BSN, OCN [00:50:10]:

I have more questions for you. The first one is a tricky one They ask, “I would be hesitant to use DESTINY-09 as first line given the side effects when PATINA has much less side effects and comparable PFS. When would you choose DESTINY-09?”

Nan Chen, MD [00:50:33]:

Did somebody take this question out of my mouth?

That is such an excellent point. DESTINY-Breast09 included patients with HR-positive, HER2-negative, as well as HR-negative, HER2-positive as well. It basically included everyone. So I agree with you.

Just to remind those of you who may not be familiar with what PATINA did: PATINA was a study in which patients received chemotherapy with Herceptin-Perjeta, so that THP, and then patients in which their cancer was resistant to that and they were HR-positive, they were started on endocrine therapy, tamoxifen, letrozole, and they actually got a CDK 4/6 inhibitor like palbociclib. That was probably the largest study that evaluated a CDK 4/6 inhibitor in HR-positive, HER2-positive patients.

The median progression-free survival, or the amount of time a disease is controlled for each patient on average, was also about 40 months. So quite similar to what we’re seeing in DESTINY-Breast09. I think you are really hitting the nail right on the head that efficacy, or how well a drug works, is certainly not the most and only thing that we think about when we’re recommending drugs or when we’re discussing drugs with our patients. Quality of life, safety, and tolerability are all really, really important things.
I personally agree with you that for most of my patients that are HR-positive, HER2-positive, I would rather choose a PATINA approach compared to this because I think the safety data is much, much better, quality of life, you’re on oral therapies, and we can always use T-DXd later on somewhere later in your therapy. Certainly for HR-negative, HER2-positive patients, for which PATINA would not be an option, I think that’s, you know, certainly an area in which DESTINY-Breast09 can be considered.

I also think, tying back into our previous conversation about safety and tolerability, T-DXd, and Caroline can speak to this as well, is definitely not the nicest drug. It’s difficult to tolerate, lots of fatigue, lots of GI side effects. I am not shy about decreasing doses, about holding doses, about doing what we need to do for patients to continue to feel well. This is a drug that definitely works very well in many patients, but it is also a drug where you can run into issues. It’s definitely a delicate balance, and making sure that we are not being too aggressive with people, because as we said, there’s no point in being too aggressive. It’s always important to balance that and make sure that patients are feeling well and doing well during treatment.

Caroline Koffke, RN, BSN, OCN [00:53:11]:

And if every oncologist could listen to their patients like you listen to yours, the world would be a better place because you take such good care.

Another question for you. So if someone progresses on THP, would you consider doing Enhertu and Perjeta? Would you reintroduce Perjeta if they progressed on HP previously or would you just do Enhertu?

Nan Chen, MD [00:53:36]:

That’s a really good question. The Perjeta, the T-DXd plus P and the THP is the same “P,” so it’s the same Perjeta, or pertuzumab, that we’re using.

I would say that if you were on THP and even on HP for a period of time and then that stopped working, I probably wouldn’t give you the pertuzumab again just because this is a drug that your cancer has seen, this is a drug that your cancer has grown on and probably developed resistance to. That being said, if there’s some scenario in which for some reason you weren’t on the pertuzumab, and as long as the reason wasn’t because the pertuzumab was giving you lots of diarrhea and causing issues, then I think it’s something that can be considered. But I would say most patients are on the HP and if you’re not on the pertuzumab, it’s more likely to be related to a side effect issue, not because we didn’t want to do it.

Caroline Koffke, RN, BSN, OCN [00:54:24]:

Got it. Someone was also asking if Phesgo alone performed better than Phesgo and Taxol.

Nan Chen, MD [00:54:31]:

Phesgo is basically a combination of the Herceptin and Perjeta. So the Herceptin and Perjeta can be given separately in IV drugs. These are bags that hang and take like half an hour to give. Phesgo is basically a shot that you can give over the course of 5 minutes. If we compare Phesgo to HP specifically, there is no difference in how well it works and there’s no difference in side effects.

What I like to say to patients is it’s purely a convenience thing. If you would like a shorter way to give you your medicine and you’re okay with shots, I think it’s a great option. I have some patients who are like, “Yes, sign me up. That sounds amazing.” And I have some patients who are like, “You know what, I don’t like shots. I’d rather just do the IV,” or “I want to do what’s worked for me.” Also totally fine and totally reasonable.

When you add the THP to HP, then you’re adding chemotherapy. You can even add the T to Phesgo. The Phesgo really is just like a different way to give the HP part.

Caroline Koffke, RN, BSN, OCN [00:55:28]:

Great, thank you so much.

And when would you give carboplatin in a THP versus a TCHP regimen? Because we know we love talking about random letters combined.

Nan Chen, MD [00:55:39]:

I know. It’s like alphabet soup. It’s not confusing at all.

I would probably say, in 2025, in the metastatic setting, there are not really a lot of scenarios in which I would use carboplatin for a HER2-positive patient.

The early-stage setting is a different story and TCHP is used pretty commonly. I think that’s a totally reasonable idea. But I probably would not use carboplatin in the metastatic setting. I’d probably just do THP.

Caroline Koffke, RN, BSN, OCN [00:56:07]:

Great. Last question. What would be your second line choice of therapy after Enhertu?

Nan Chen, MD [00:56:13]:

Oh my goodness. That is truly the million-dollar question in HER2- positive breast cancer right now. We actually do not have any drugs, in a large clinical study like the ones I’ve shown, that has demonstrated performance after T-DXd.

There are many other options of things we can do. For example, some patients can get THP after T-DXd, For example, in the study, if you got T-DXd first, you can also give other drugs such as T-DM1 or Kadcyla. You can also do tucatinib [Tukysa], which is another HER2 blocker that comes in a pill, and you can combine that with chemo and other things that go together. The reality is, is that none of those regimens were actually evaluated in patients who already received T-DXd, and so we don’t totally know how they perform. However, in 2025 we have to work with what we have to work with.

I would say it depends on the patient. Certainly if someone has brain disease and I’m really worried and wanting to make sure that we’re giving something that can cross the blood-brain barrier, I would probably reach for a drug like tucatinib in order to make sure that we’re keeping up with that. In a patient who doesn’t have that, I think everything else is fair game. I think going to THP if you use T-DXd first is reasonable. T-DM1 is reasonable. There are a lot of really excellent HER2 agents that are in earlier phase development than this, and there’s a lot of clinical trials and I think those are really good options as well.

Caroline Koffke, RN, BSN, OCN [00:57:44]:

Great. Thank you. All right, I’ll let you take it away with TNBC.

Nan Chen, MD [00:57:47]:

Great. Let’s do it.

The ASCENT-04 study is a little bit similar to DESTNY-Breast09 in that it’s evaluating a drug that we already use in triple-negative breast cancer and trying to see should we use it earlier. This study is sacituzumab govitecan [Trodelvy] plus pembrolizumab versus chemotherapy plus pembrolizumab in patients with previously untreated PD-L1 positive advanced TNBC.

Metastatic TNBC for a very long time was treated purely with chemotherapy. Frankly chemotherapy did not work very well, and we were doing a horrible job taking care of our patients. A few years ago we realized that immunotherapy may have a role in these patients, and so we did some studies evaluating whether immunotherapy would be beneficial and in which patients it would be beneficial. What came out of those studies is a flag called PD-L1, so this is a flag just like HR is a flag just like HER2 is a flag, but it’s a different flag. In patients with a lot of PD-L1 flags, giving immunotherapy such as pembrolizumab was really helpful. But in patients who did not have a lot of PD-L1, so they’re what we call PD-L1 negative, giving them pembrolizumab was not that helpful.
Nonetheless, even in patients who got pembrolizumab with chemo, their cancer was under control for still about 9 months or so, which is better than what we were doing before but still not where we want it to be. So there’s a lot of room for improvement in this.

Sacituzumab govitecan is what’s called a Trop-2 antibody-drug conjugate. If you think about this drug like a missile, Trop-2 is the target that it’s going after and then it has a chemotherapy payload. So it basically holds its chemotherapy tight until it gets to the flag, meets up with the flag, gets ingested by the cell and then releases the chemo locally, specifically in the area where the tumor is.

Sacituzumab govitecan has been used in in triple-negative breast cancer for the last few years. It has shown that in second line and beyond it is better than chemo. It helps patients stay alive longer than chemo. It helps patients control their cancer for longer than chemo.

What the study looked at is patients who are PD-L1 positive, so have a lot of that PD-L1 flag, and have not had treatment for metastatic TNBC. They were randomized to receive either chemotherapy or pembrolizumab or to receive sacituzumab with pembrolizumab. Basically replacing the chemo with sacituzumab.

Overall, the patient populations are pretty similar between the two groups. Only about a third of these patients had what we called de novo triple-negative breast cancer, meaning that their cancer at diagnosis was already metastatic. Most of these patients actually had early-stage breast cancer and then unfortunately their breast cancer came back. About half the patients in the study, their cancer came back over 12 months later, and about 20% of the study, their cancer came back pretty quickly within 6 to 12 months.

We’re looking again at progression-free survival, which is the amount of time that the cancer is controlled before we have to move on to another therapy. The blue line is sacituzumab and the red line is chemo. And we see that sacituzumab keeps the cancer under control better than chemotherapy. specifically for about 11.2 months compared to 7.8 months. At 6 months, the percentage of patients who were still on therapy was about 72% on the sacituzumab arm and 63% on the chemo arm. At 1 year, a little bit less than half the patients were still on sacituzumab whereas only a third of patients were still on their chemo and pembrolizumab.

What we see is not only did it keep the cancer controlled, but the duration of the response was also better in sacituzumab compared to chemotherapy. And then more patients had their cancer decrease. The objective response rate is the proportion of patients where their cancer either, basically their cancer declined by over 30%. About 60% of patients had that happen with sacituzumab and only about 53% of patients in chemo.

Similar to what we saw in DESTINY-Breast09, about a similar portion of patients had what we call a partial response, meaning that their cancer decreased by over 30% but not completely, but 13% of patients had their cancer disappear with sacituzumab and pembrolizumab versus only 8% of patients had that happen with chemo and pembrolizumab. In many different measures of how we evaluate whether a drug is better or not, sacituzumab performed better than chemotherapy.

Looking at side effects, sacituzumab is a drug that we’ve been using for quite some time in triple-negative breast cancer and now we actually also use it in HR-positive breast cancer as well. This is definitely a drug that has side effects. Part of the drug, that payload part, is chemotherapy, so many patients experience neutropenia, or that decreased white count, as well as fatigue, nausea, diarrhea. Similar to previous studies with sacituzumab and our clinical experience and real world experience, this is not that much different than what we already know about the drug. Not anything new or not anything inconsistent here.

Ultimately the ASCENT-04 study was the first randomized phase III study to evaluate the efficacy and safety of an ADC with a checkpoint inhibitor such as pembrolizumab for first-line treatment in PD-L1 positive metastatic TNBC. It did lead to an improvement in how long the cancer was controlled, 11.2 months compared to 7.8 months. They are looking at overall survival data, or how long patients lived, but we don’t have that data yet. They did see an increased complete response rate and that the safety profile of sacituzumab plus pembrolizumab was consistent with the known profiles of either agent. And no new safety signals were observed.

Caroline Koffke, RN, BSN, OCN [01:04:08]:

I actually don’t see any super specific questions about TNBC, but I do want to ask. You’ve done a really nice job of explaining the importance of talking to your oncologist. Is this right for you? Do you have a mutation that’s actionable? Where is your cancer?

There’s so many different unique things that make your cancer unique to you, and having those conversations about whether a trial is right is super important. And we’re happy to provide more resources on that as well. But I did actually want to ask you two I think really important questions before we dive in, that are a little more general. Have you seen any noticeable decrease in research studies and FDA approval times because of cuts at the NIH [National Institutes of Health] or CDC [Centers for Disease Control]? I know this is top of mind in your field right now.

Nan Chen, MD [01:04:58]:

A hundred percent. I think that everyone in our field is obviously really concerned about this. To be honest, I think that the time that this has been going on is a little bit too short for us to really know what the effects are. This is a question that I’ll probably have a better answer to in like another year or 18 months.

Obviously, coming from an oncologist, I think it is of the utmost importance that we make sure that our patients have access to the best things that we have. And we all know, as you guys all do too, that time can, for many people, be of the essence. I have gotten things approved through insurance without the actual FDA approval, with just positive data. And so that would be an option to discuss with your oncologist, whether they’d be willing to go to bat for you, even if it’s not quite approved yet, to see if your insurance would still allow you to receive these medicines because we have positive data and because we know that these drugs are better. So that’s one option. But it’s certainly something that’s concerning and, in the current climate, something that we’re thinking about as well.

Caroline Koffke, RN, BSN, OCN [01:06:06]:

Thank you. And I think you bring up a really amazing point, and it just highlights how impactful you are with your patients. Finding a doctor who will go above and beyond to talk to these big companies to get approvals when approval might not be coming from the federal government is so important. And that is an option. People should feel empowered to get that second opinion and find those doctors who are able to go to bat with insurance companies in order to make sure you’re getting the treatment that you deserve.

Nan Chen, MD [01:06:36]:

Caroline and I both have had patients where we actually got compassionate use of the drug from the drug company that makes the drug itself. Sometimes it is a dead end, but just to say that there are multiple avenues that we can explore. If it’s a situation in which it makes sense to do it, talk to your oncologist, get a second opinion, do what you need to do to make sure that we are exploring all of those options.

Caroline Koffke, RN, BSN, OCN [01:06:59]:

Absolutely. It’s a really important time for advocacy.

Another question, and then I’ll let you talk about how to talk to your doctor about a clinical trial. But did you see anything at ASCO talking about the increasing rates of cancer in younger women? I know we saw this all the time in clinic and it’s frightening.

Nan Chen, MD [01:07:19]:

Unfortunately this is a trend that we’re not only seeing in breast cancer, but we’re seeing in a lot of other cancers as well. I think that from an academic university side, there’s obviously a huge interest in trying to understand why this is happening, whether this is kind of something unique about each cancer or there are ways about our lifestyle or changes that are happening that are causing cancer to be diagnosed in younger folks. I don’t recall seeing anything specifically at ASCO that addresses this, but I do see this as an ongoing area of research. And I would definitely expect to see more things in the next 3 to 5 years.

Caroline Koffke, RN, BSN, OCN [01:07:55]:

Great. Well I’ll let you briefly run through talking about clinical trials and then I will send us off.

Nan Chen, MD [01:08:01]:

Yeah, I think it’s always a really important question to consider whether a clinical trial is right for you. The most important thing I would say is talk to your oncologist. They are your best resource. Some example questions you can ask them are: Is there a clinical trial that you can suggest for me? Can you provide additional information about this trial? Sometimes in clinical trials you may have to come in more frequently than you otherwise would. So how often will I have to be seen? What are the side effects I may experience? Does it include a placebo? Will I get one? And then, we want to be very realistic: What costs are covered by the trial?

All of these questions and many, many more are totally valid questions for your oncologist. And these are questions that I get all the time. I might not be the best person to answer them, but your oncologist should have a clinical team that may include a nurse, a research coordinator, managers, other people who can help you figure out the clearest idea of whether or not a clinical trial is the best option for you.

Here are just a couple resources of places where they list a lot of different clinical trials. Admittedly, these websites are a little bit overbearing, so again, talk to your oncologist and use them to help guide you through these resources as well.

Just to elaborate that a lot of the clinical trials we discussed involve using new therapies or using them differently, but there’s tons of other research that’s going on locally, here at the University of Chicago, but all over the country. A lot of studies will collect blood, collect stool, and collect tissue to really understand how these things are changing with therapy. And this is just as important as new therapies to help us understand how we’re doing with what we’re giving.

Lastly, quality of life is so incredibly important. So there’s lots and lots of research evaluating quality of life specifically, and these are also ways to get involved with research and get involved and see if there are studies that your oncologist can recommend for this as well.

Thank you, everybody, so, so much. This has been such a wonderful evening and I’m so, so glad that all of you were able to spend it with me. If you have any further questions, please reach out to Caroline and them, but it was such a pleasure to speak to everyone today.

Caroline Koffke, RN, BSN, OCN [01:10:03]:

Dr. Chen, you are an absolute gem. You are so full of knowledge, so caring for your patients. I know we didn’t get to answer everyone’s questions tonight, I know we didn’t get to talk about every trial, but you did such a nice job of highlighting the immense amount of information and very, very high level information that came out of ASCO. So thank you.