Episode 54: Updates from ESMO Breast 2026 in Berlin

Dr. Rani Bansal of Duke University joins the show to share her insights on the latest ESMO Breast meeting that concluded in Berlin. Dr. Rani shares data on the top 5 abstracts that may change or inform practice.

Check it out, share, subscribe, and join the conversation.

Transcript

SPEAKER_01 0:01

Welcome to the Healthcare Unfiltered Express, where I conduct short video interviews packed with relevant and timely information that you cannot miss. So sit back and enjoy the show. Ronnie, it's your first time on one of my shows, Healthcare Unfiltered Express. Thank you so much for joining me.

SPEAKER_00 0:21

Thank you for having me.

SPEAKER_01 0:23

And congrats on everything that you're doing at Duke. Um, so um we want to just uh dive right in. So Esmo Berlin, Esmo Breast in Berlin, just concluded a lot of information and data coming out of it. And uh I've asked you the difficult task, which is what clinicians must know about what was presented at Esmo Berlin. So let's get started. Number one.

SPEAKER_00 0:46

Yeah, number one. So I think um the first kind of group of trials, or in my opinion, was looking at antibody drug conjugates after prior antibody drug conjugates. So the first trial was the Ceteen trial that was presented by Dr. Tarantino. Um, this trial was a small um phase two trial that looked at patients who had previously who had metastatic HER2-positive breast cancer, who had previously had TDXD. And then patients were going on SASTUSMAP gobatican, so a trope 2 antibody drug conjugate with trestus mab. Um, and I really thought this trial was really interesting. We think that TDXD causes a lot of downregulation of HER2. Um, and so using a different type of ADC makes sense. Um, but unfortunately, this is actually a negative trial. Um, only one patient, I believe, out of the 20-ish patients that were on trial even had a partial response. So only about a 3% overall response rate. Um, and really not much benefit in terms of progression-free survival. So I think really just showing us that we don't sequencing an antibody drug conjugate after patients have already received an antibody drug conjugate that's a similar payload probably doesn't have much benefit for our patients. Um, and we need more drugs in this space.

SPEAKER_01 1:57

Uh, you said the same payload. You think if it was a different ADC with different payload, we don't know the answer to that. Is that fair?

SPEAKER_00 2:03

We don't know the answer. I think that's what we're really excited about, like for the future, is different antibody drug conjugates with new payloads, so not topo one payloads. Um, I think that is hopefully what we'll see a response.

SPEAKER_01 2:16

Because the TDXD and the SG are the same payload, right?

SPEAKER_00 2:19

Topo one, yeah, exactly. They're different targets, so HER2 versus Trope 2, but it wasn't enough to show benefit. Um I think still important trial, even though it was negative. I think we learn a lot from negative trials. Um, the other trial similarly was an update on HER3 DXD. So it's another ADC. Um, and it was presented by Dr. Hamilton, and it looked at um using HER3 DXD after prior patients had received prior ADCs in metastatic breast cancer. So there were different cohorts. Um, there was a cohort that had not received prior ADC, and then there were cohorts within triple negative breast cancer that had received prior ADC within HER2 positive, as well as HR positive HER2 negative. And overall, big picture again, we did not see much benefit for patients in regards to progression-free survival with receiving a subsequent ADC, even with a HER3 ADC. Um, again, this ADC is a DXD component, so it's a topo one, so similar payload class. So kind of showed again that sequencing of ADCs, the the next one you use, you're not really gonna get much benefit from for patients, unfortunately.

SPEAKER_01 3:30

So that that's interesting. You think those two, the Satine and this one, kind of saying the same message?

SPEAKER_00 3:37

Yeah, I think that, you know, this is finally like we're starting to see now prospective trials, small trials, like 20, 30 patients, but still really like interesting data showing us that really the second ADC that we use, we are not getting as much benefit from the first that we had used for patients. And I think this is really important because we keep seeing more and more approvals come out for these ADCs. But we when we sequence them, we don't see that benefit after patients have received a prior. So I think we just need different drugs. I think we now are crowding the space with a similar type of ADC, and we really need to start thinking, you know, okay, how can we get new drugs that are gonna work differently?

SPEAKER_01 4:18

Absolutely. Great. Number three.

SPEAKER_00 4:21

Okay, number three. So for me, I'm really interested in young breast cancer. So the pre-Coupera trial was really interesting to me. It was looking at girodesterin, which is an oral SERD, um, in a window, kind of a window opportunity. So as a neoadjuvant therapy, testing it in pre-menopausal patients, really to see can these patients um not need ovarian suppression? So it had an arm that had giridestrin alone and then gerodesterin with ovarian suppression compared to an AI with ovarian suppression. And it was a non-inferior trial. So, really just trying to look at in terms of changes in KI-67 estrogen pathway, is there similarity between gerodesterin alone versus with ovarian suppression? And it was negative. It did show that the addition of ovarian suppression does decrease KI-67 and it didn't meet the non-inferiority. But I think for me, I think it still shows that this class is still active for pre-menopausal patients, and there may be some patients that still benefit getting a single agent oral CERD without ovarian suppression. Um, I just think we need more data. Yeah.

SPEAKER_01 5:25

Running in this trial, they gave premenopausal women AI without ovarian suppression? With ovarian suppression.

SPEAKER_00 5:33

So it was three groups. Um, AI with ovarian suppression, giridestrin with ovarian suppression, and then gerodestrin alone.

SPEAKER_01 5:40

I see.

SPEAKER_00 5:40

And so the thought was like, are oral SERDs, like, can we finally, you know, have an equivalency in terms of without ovarian suppression for premenopausal patients? Because it's a whole new class of drugs that I think we'll probably see an approval for either this year or next year in the adjuvant setting. And so I think that's where it's a big deal. Like, are there patients that are pre-menopausal that we can give this drug like we give tamoxifen without ovarian suppression? And I think the answer is yes. I think we need more data on it. But I think I have patients that can't tolerate ovarian suppression. And I would love to be able to offer them an oral CERD without ovarian suppression.

SPEAKER_01 6:18

And and uh in the US at least, uh for the breast oncologists, ovarian suppression, what what's most oncologists using?

SPEAKER_00 6:27

Um, so well, uh most oncologists, luprod or ghoserolin are the two um most commonly used for our patients. Um there is a lot of data that ovarian suppression does benefit premenopausal patients. So I'm not saying, you know, that it's not important for these patients, but it comes with a lot of side effects. Yeah. And I think that's where I have patients who struggle to stay on it and then they come off of it, and then I can't offer them an AI. So I'm only left with tumoxaven. And I think that's where I'm really excited for this new drug class. So we have another option for our premenopausal patients.

SPEAKER_01 7:00

Great. Number four.

SPEAKER_00 7:02

Um, number four, I would say the train four um trial was really interesting. So, what I liked about this trial was it's a neoadjuvant trial for HER2-positive breast cancer, stages two or three, small trial, um, but looked at a chemo-free neoadjuvant regimen. So they used to catnib with um trestuzimab and pertusimab, and it showed a pretty significant path CR rate, uh, pathologic complete response rate, comparable to chemotherapy within the 70% range. And so I think this is really interesting data showing how we can maybe treat some patients in the neoadjuvant setting without any chemotherapy. And I think this is really interesting because it comes in a time where we also saw DB11, Destiny Breast 11, being presented, showing that we are escalating therapy for some patients using an antibody drug conjugate in the neoadjuvant setting with TDXD. And now we have this data showing a chemo-free regimen that also has a very good PATCR rate. So it I think it's getting really complicated in the HER2 positive space, which is great for our patients. But now we're seeing different trials showing we can de-escalate with really good responses, and then other trials showing that we should be escalating. So I think this data is just really intriguing. And I think we are gonna need to start having trials like directly comparing or better stratifying patients in terms of how we should approach HER2-positive disease, localized disease.

SPEAKER_01 8:35

Today, when a patient walks in the door seeing you with this phenotype and genotype with the HER2-positive disease, what are you doing?

SPEAKER_00 8:44

Okay, so this is a great question, um, and a lot of controversy over this right now. And this is um something actually me and my team at Duke have been talking a lot about. Um, we are doing an adaptive approach. So pretty much I am looking, so patients that have a stage two to three breast cancer that would meet criteria for DB11, so large, very large tumor inflammatory breast cancer or lymph node positive disease. Um, I am starting with a chemo, so THP regimen, and then I am following them. I'm getting baseline CT DNA and then repeating an MRI uh of their breast at the halfway point, and then deciding if I need to escalate to TDXD or if I can continue on their current treatment plan.

SPEAKER_01 9:30

Interesting. Well, that's a probably a good segue on the CT DNA, though.

SPEAKER_00 9:34

Yeah, so um other um there are many different trials at um ESMO breasts looking at CT DNA. One I think that was discussed a lot was the update from Serena 6, just looking at um ESR1 testing in those patients in that trial. So um Serena 6 looked at um following ESR1 mutation development for patients um on their um AI and CDK46 inhibitor. And what was interesting showed that about 20% of patients had a positive um like flip to ESR1 mutation detection within that first year. Then the rest of the patients that did that detection did take longer within years after. And so I think, you know, the FDA has weighed in on this a little bit and has not, you know, we don't yet have an approval for kind of this the regimen and the way the trial was um done for Serena 6. So I think there's still a lot of gray area on how we should be following CT DNA testing, at least in the metastatic setting, and how we should change therapy based on development of certain mutations like ESR1.

SPEAKER_01 10:36

Ronnie, you you are using CT DNA today in your clinical practice outside of trials?

SPEAKER_00 10:43

I am using it in very specific cases, yes.

SPEAKER_01 10:48

Can you give me a use case? Like just an example?

SPEAKER_00 10:50

So, as an example, um in the in the localized setting, um, like I just mentioned, I'm starting to try to think about how to use CTDNA to help guide how I approach therapies in the neoadjuvant setting. Um there are many, um, there's a lot of data coming out that CTDNA, even for patients that have residual disease after surgery, if CTDNA is positive or negative, that can really inform us about their prognosis, maybe even better than what their residual disease showed. Um, and so that's where, like I, the example I just gave in the HERTI-positive setting, I'm starting to use it as upfront, seeing if patients are CTNA positive, and then if they clear while they're on their neoadjunct therapy, feeling comfortable maybe not escalating their therapy and maybe being able to de-escalate. Again, this is my clinical practice of how I'm interpreting this data. I'm hoping we get more studies in this, but like in real time, I don't have the trials with this information. So, in real time, I'm trying to figure out how I can incorporate all of this data into what we do in practice. Um, I think in the metastatic setting, CT DNA is a great um kind of like a tumor marker to use to follow patients. I think outside of that, I'm not really using it yet to change my therapy. So I'm using CTDNA more to follow patients as their disease course, but I haven't been using it to change how I treat them unless they're progressing on imaging.

SPEAKER_01 12:12

Yeah. We've got room for one more if you've got one more, unless this is these sort of the top ones that you wanted to talk about.

SPEAKER_00 12:18

Oh, um, I think for me, these were the top ones that I want to talk about. I think there was um also, you know, an update for the Capitello trial. It did not show um a significant overall survival benefit. However, it wasn't powered for that. What's the capitolo? The capitalo trial is the use of um cap Piva Certib um with fulvestrant um for second for patients that have a PIC3CA um mutated breast cancer. Um, and so we know there's a significant progression-free survival benefit, but this was now the overall survival um update, and there wasn't a difference there. I think it's complicated for um these, you know, trials in the ER-positive HER2 negative metastatic space. Um, I think there's a lot of differences a lot of time between the groups, especially in the control group with what they get subsequent therapies-wise. Um, I clinically have seen a lot of my patients do well on capiva assertive. So I still um, you know, and believe in the drug even without an overall survival benefit. Um, but that was just another, I think, interesting trial that, you know, even though we saw such a great PFS benefit, it didn't correlate to an overall survival difference.

unknown 13:29

Dr.

SPEAKER_01 13:30

Ronnie Bansal, it's wonderful to see you. And it's uh thank you so much for simplifying what is becoming a very complex topic. You gotta promise me after your maternity leave, you're coming back. So you could uh yes. All right. No, I will.

SPEAKER_00 13:43

And there's gonna be so much more. I'm so excited for everything that's going on in the world of breast cancer.

SPEAKER_01 13:47

You're on the record that you're coming back. Dr. Ronnie Bansal on Healthcare Unfiltered Express. Thank you so much.

SPEAKER_00 13:53

Thank you.

SPEAKER_01 13:54

Thank you for listening to this edition of Healthcare Unfiltered Express. Until next time, take care.