New Approvals for Breast Cancer

Hinzugefügt: 2026-05-28

[00:00:01]Welcome to the Healthcare Unfiltered Express, where I conduct short video interviews packed with relevant and timely information that you cannot miss.

[00:00:11]So, sit back and enjoy the show.

[00:00:20]Well, excited to have you back, Virginia. Thank you so much for coming on Healthcare Unfiltered Express. You always are very generous with your time, despite how busy you are.

[00:00:28]But, that's a testament that you love teaching people and you love sharing knowledge with people. So, thank you.

[00:00:34]Thank you. I just love talking to you, Charlie. I love talking to you as well.

[00:00:37]And we're taping this before ASCO, and we are going to actually air it even before ASCO, because certain things just can't wait. And I've asked you to come on the show to talk a bit about some approvals, recent approvals that came on in breast cancer. We're going to try to put those in context of managing breast cancer as a disease, whether it's early stage or late stage. So, what are these new approvals that we just heard about over the past week or so?

[00:01:02]So, what the FDA did was it took two clinical trials, the Destiny Breast 11 and the Destiny Breast 05, that looked at the early stage incorporation of TDXd into the treatment of her positive breast cancer, and then approved TDXd in that early stage setting. So, just a reminder to to the viewers, DB 11 was a new adjuvant trial. It had three arms.

[00:01:25]The first arm was the standard of care ACTHPR.

[00:01:28]And then, the second arm was TDXd for eight cycles. That arm did not meet the the pre-specified endpoints, and so the efficacy data has not been presented yet. But then, there was the second investigational arm, which was TDXd for four cycles followed followed by THP for four cycles. And what the trial showed, and it was presented last late last year, was that the arm of TDXd followed by THP had an improvement in pathological complete response compared to TCA to ACTHP.

[00:02:00]There was some update recently looking at the RCB rate and that also was was increased compared to in the TDXd arm.

[00:02:08]Now, there's no long-term data from this study yet. It's not mature enough.

[00:02:13]Uh but that's why the FDA was looking at the Destiny Breast 05 trial, which was the adjuvant use of TDXd. So, here we're taking patients that have received new adjuvant therapy, have residual disease at the time of surgery, and then go on to either receive TDM1 per the Catherine trial, which is a standard of care, or receive TDXd. And these were high-risk patients. And uh the trial showed that there was an improvement uh in uh in event-free survival with the use of TDXd compared to TDM1.

[00:02:44]So, they took both of these trials that showed that that showed that TDXd is superior to just standard of care ADC or chemo and approved TDXd in this setting.

[00:02:53]I It's great for our patients. I think it raises a big question where How do we use TDXd now? Do we use it in the new adjuvant setting or do we use it in the adjuvant setting? And I think you're going to hear debates about each one of these approaches for the next year or so until we have event-free survival data from Destiny Breast 11.

[00:03:13]So, the approval is for new adjuvant and adjuvant. Correct.

[00:03:18]Okay. So, but but but essentially you can give it Is it that you have to do new adjuvant and adjuvant or you could choose and mix? You do new adjuvant Well, you're going to have to choose one of the two approaches and that's the unfortunate uh thing about these trials cuz they were independent trials. So, if you decide to use it new adjuvantly, you know, the argument that people make is first of all, it's just four cycles of TDXd followed by THP. So, the safety is much better with that approach. You have a 67% uh PCR rate with that approach, which is much higher in the ER negative compared to the ER positive, it's around 80% in the ER negative HER2 positives, 50% in the in the triple positives. And if you do achieve PCR, that's great. You can just give HP in the adjuvant setting.

[00:04:05]Now the [clears throat] question is, what if you do not achieve PCR? Then what do you do adjuvantly? Do you give more TDXd? We don't have any data. Do you give T-DM1? And we don't really have data of the efficacy of T-DM1 after TDXd. So that's really the the concern with that approach. Now with the with the Destiny Breast 05 approach, you just give whatever new adjuvant therapy you want to, which, you know, in this country most of us would be giving TCHP for six cycles. And then if there is residual disease, which is again around 40% of patients, then you give TDXd, but now you give it for 14 cycles. So a lot more exposure to TDXd compared to the the Destiny Breast 11 approach where you just give four four cycles of of TDXd.

[00:04:51]So it's a little, you know, the inclusion criteria are a little different. The FDA didn't really go into all that, just at high risk. Uh but if you look at the inclusion criteria for the Destiny Breast 05 trial, these were patients that had either inflammatory breast cancer, node-positive disease at the time of presentation, or inoperable breast cancer to start with. So these were your very high-risk HER2-positive breast cancer patients.

[00:05:15]So a a general oncologist who's not seeing breast cancer only, who's just seeing is a general oncologist, how do you think what do you predict how they're going to take this data and how they're going to approach patients? Because I think real-world data will be interesting with this information you described.

[00:05:34]Actually, I'm trying to put the hat of a general oncologist.

[00:05:37]Uh I'm you know, some of them will be calling you and say, "Hey, what should I do?" But but some will probably, I don't know.

[00:05:45]I I think there's such a such a big movement toward antibody drug conjugates this day these days. There's the the the responses and the and the benefit from TDXd as well as others has been so big that our general oncologists love using them. So, I have the feeling many of them will try the new adjuvant approach [clears throat] giving TDXd for four cycles followed by THP. That's also an anthracycline-free regimen.

[00:06:10]Um you can always make the argument if you don't get a PCR, you can just give AC adjuvantly. There's a lot of different approaches people will do.

[00:06:17]Just a reminder that none of this was built into the clinical trial. Yeah. And also that we don't have long-term outcomes with with this approach. Um so I I I I >> some people will get TDXd adjuvantly if they don't have PCR.

[00:06:32]That's what I will likely uh um move towards until we get the the the long-term data from Destiny Breast 11 approach uh because we do have longer uh data with uh DBO5.

[00:06:46]Great approval is helpful for patients as you said. May create some temporary confusion, I think. Hopefully this will uh the dust will settle.

[00:06:53]But maybe sticking on the theme of uh either ADCs or something else, uh we just recently had the ASCO Breast also concluded. Anything that might that uh intrigued you aligned with uh ADCs specifically TDXd anything that might kind of like have the same theme?

[00:07:12]I think yeah. So, the Saci trial was presented, which is a smaller trial, a phase two trial, but it looked at HER2-positive breast cancer patients that had received TDXd. And after progression on TDXd, they were given sacituzumab govitecan plus trastuzumab.

[00:07:27]Now, this is the first data that we have on sacituzumab in HER2-positive disease, uh but obviously sacituzumab does, you know, targets um uh Trop-2. So, and we know that there's Trop-2 receptors in in any breast cancer including HER2-positive. So, the the the trial was very disappointing, but taught us a lot of lessons. So, when you look at the response rate from the trial, only 3.7% response rate with sacituzumab.

[00:07:52]Progression-free survival, 2.3 months.

[00:07:55]So, so basically, this approach did not work. And this is really the first clinical trial data that we have on ADC followed by ADC. And the lesson that we're learning is that if you have an ADC with the same target, and the target being a topoisomerase 1 inhibitor, and the patient's cancer has already progressed on one topo 1 inhibitor, the likelihood of having a response with the second one is really low.

[00:08:21]And and I'm not sure why it's taken us all of these years to figure this out, because we've known this with chemotherapy for a long time. We don't usually give docetaxel after paclitaxel, because we the target is the same. So, I this is a valuable lesson. This is also important for the pharmaceutical industry to start looking at ADCs that do not use topoisomerase 1 inhibitors as their payload, because it's important that that we find better ways of sequencing these ADCs. But you could imagine ADC that has a different payload may work after another ADC. Absolutely.

[00:08:58]And this is where the mechanisms of resistance of ADCs come to play. We know that one of the mechanisms is the topo 1 mutations, but obviously, another mechanism is her2 mutations or trop-2 mutations and so forth. So, if in the future, you know, we we have a nice tool that shows us in real time what the generation of mutations is, then that'll help us find a better ADC approach. But but right now, we don't we don't have that. We can't predict that in real time.

[00:09:29]Anything else?

[00:09:31]Um another interesting data set was from the pre copera study. This was a window of opportunity trial in patients that have estrogen positive early stage breast cancer with the use of of giredestrant. And they looked at giredestrant in premenopausal women with and without an LHRH agonist as well as an AI with an with an LHRH agonist. And the bottom line is, as predicted, if you give giredestrant with an LHRH agonist, you're decreasing the Ki67 more. Um and and so, you know, we've kind of suspected that, but we also know that some patients may not be able to tolerate ovarian suppression. And in those patients, the use of giredestrant by itself still decrease the Ki67, just not as much as uh in the patients that also had uh received an LHRH agonist. So, I think again, this is a nice small study, uh thought-provoking, and and and will help us in the future in how we plan uh to to to use these oral SERDs a little bit better.

[00:10:36]Yeah, I'm I'm very interested in oral SERDs because they're like completely seemed like a new class that's going to really take over pretty much the entire world of breast cancer.

[00:10:45]Uh anything else before I let you go back to your busy schedule? I I think the last uh study that I liked was the track ER study. And this was a study in patients with high-risk disease, ER positive breast cancer early stage setting. And they looked at ctDNA. So, the the the the role of MRD. And a couple of interesting things that came from this. So, even though this was a high-risk patient population, four more positive lymph nodes, one to three positive lymph nodes with high-risk features, more than 5 cm tumors, only 11.6% of these patients actually had or at some point had a positive ctDNA test.

[00:11:20]So, a very small number. Out of those 11%, 42% already had positive scans at the time of a positive ctDNA test.

[00:11:31]The majority of those had distant disease, 87%. So, there were some local recurrences that were caught with that approach, but the majority was metastatic disease. So, this study is also going to be randomizing patients to receiving a CDK4/6 inhibitor or not. So, we'll see some long longer term results from the study, but this is something that we need to think about, especially for the people that are already using MRD in breast cancer, because we do not have any predictive data. We have prognostic data, and and this study confirms the the prognostic significance of MRD, but no predictive data. We don't know what to do if there's a positive ctDNA test.

[00:12:10]So, in my practice, I don't usually I don't use MRD.

[00:12:15]Before I let you go, just one quick thing because I So, only 41% of patients with ctDNA positive had positive scans. The remainder was a ctDNA positive false positive?

[00:12:29]Yeah.

[00:12:30]They had positive scans at the time of the first ctDNA positive result.

[00:12:35]There's usually there's a lag time, and for ER positive disease, it's longer than for triple negative. For triple negative, around 70 to 80% of these patients will have positive scans. So, at some point, these patients, the majority will develop metastatic disease, but not at the time of diagnosis of of that positive ctDNA. And so, the thought is maybe we can salvage the patients by changing endocrine therapy. We don't have those results yet, but hopefully they'll get generated in the future.

[00:13:02]Yeah. Well, I'll stay I'm going to try to be not biased, but I I do think in the future that is going to move from prognostic to predictive. Today, you're absolutely correct. It's we don't have that data, but it's hard to believe that we It is disease. I mean, ctDNA positivity is actual disease. It's a matter whether you need to intervene today or tomorrow kind of thing. Agreed.

[00:13:25]Dr. Virginia Kaklamani, always wonderful to have you on Healthcare Unfiltered Express. Thank you.

[00:13:31]Thank you so much.

[00:13:33]Thank you [music] for listening to this edition of the Healthcare Unfiltered Express.

[00:13:38]Until next time. Take care.