November 29, 2023. “Updates from ESMO 2023”
Dr. Hope Rugo moderated the virtual UCSF Bay Area Breast Cancer Forum to discuss results from the recent European Society for Medical Oncology 2023 Virtual Congress.
ESMO’s core mission is to improve the quality of cancer care, from prevention and diagnosis all the way to palliative care and patient follow-up. It is to educate – doctors, cancer patients, and the general public – on the best practices and latest advances in oncology. The ESMO Virtual Congress 2020 presented promising new developments aimed at improving cancer patient care.
Hope Rugo, MD: Welcome, everybody to the UCSF Bay Area breast cancer forum. And we’re really excited to have you here and excited about our discussion today, which is to talk about some of the updates presented at the European Society medical oncology meetings. I’m Hope RUCO breasts medical oncologist at
The University of California San Francisco’s Comprehensive Cancer Center. And I’m joined by my colleagues, Dr. Laura Huppert, who is a faculty member in breast oncology, and Dr. Saya Jacob, who’s a Senior Fellow in our breast oncology program. And then of course, we wouldn’t have the forum with our melody Gullu,
Who’s coordinated and organized the forum as a volunteer for now’s quite some number of years. So the way our forum works, and we’re really happy to welcome you here is that we welcome your comments and thoughts. If you look at the
Bottom of the screen, you can see a q&a button, use the q&a button to put in questions. And we’ll keep an eye on them. And we will also answer them live if we can. And otherwise, we’ll type in the answers the chat button really only if you’re
Having some trouble hearing or something like that. Otherwise, q&a for all the questions regarding our comments and presentations. We’d also love to hear from you about what topics you’re interested in for the forum in the future, what you like what you don’t like, and anything else you want to tell
Us about. We will do our next. Our next forum, we’ll be focusing on the San Antonio Breast Cancer meetings, which will be next week starting on Tuesday. And they run through Friday. And we have lots of really interesting data that will be presented there. So we look forward to talking to you
About that meeting in early January. We haven’t exactly set the date yet, but it probably will be January 10. We do these usually on Wednesdays from six to 7:30pm. So we look forward to talking to you today Dr. Huppert actually is discussing some
Additional data from this, these trials at our San Antonio Breast Cancer meetings. But at ESMO, we saw results from two randomized trials that looked at giving immunotherapy to patients with a different disease subset. So immunotherapy now has been shown to improve outcome for patients who have more, you know, a
Little bit more triple negative breast cancer in the early stage setting. So cancer in lymph nodes or large tumors that are triple negative ERP or too negative. But there was a lot of interest in looking at more aggressive hormone receptor positive cancers, because that represents 70% of all breast
Cancers. And a subset of those cancers aren’t slow growing, but are more fast growing, tend to occur more in younger women. So these trials actually looked at hormone receptor positive breast cancer to see whether or not immunotherapy could help those trials. So I’ll let Laura talk now about those trials and the
Interesting data. And we really look forward to your questions and thoughts as we go and one of the questions that came up is will you send a link with the archive of these farms following the call? And melody? We’ll answer that because there is a
Link that’s on our website. And also, if you look up the Bay Area, breast cancer forum it out, you can find that if you use the email that’s on there was on your screen, and it’s still in the in the pictures of people. It’s Melody’s avatar. If
You email there, you can get the link as well. So we’ll talk more about that. And we appreciate your questions. Even if they weren’t areas that we were going to discuss. We will talk about them. So the podium is yours, Laura. Wonderful.
Laura Huppert, MD: Well, thank you all so much for being here tonight. And I have the pleasure of discussing two separate abstracts which are both somewhat similar. So I’ll go through them both but as hope mentioned, they’re both looking at the use of immunotherapy for hormone receptor positive her to
Negative early stage breast cancer. So there’s potentially a new patient population that could benefit from this class of medications. And briefly by way of background, just to remind people what immunotherapy is, is we have different classes of cancer directed medications, so chemo therapies and different therapies and immunotherapies are basically targeting the
Immune system to rev up the body’s immune system to help fight cancer and it’s currently Pember lism AB one immune immunotherapy drug is approved for triple negative early stage in metastatic setting and as of now there are no approved immunotherapy indications for ER positive breast cancer and so
Both of these two trials that I’ll talk about today are looking at immunotherapy in this patient population in combination with chemo so as I just mentioned, ER positive or negative breast cancer is a new Two common subtype of breast cancer and some of them are slower growing where the
Patients don’t need chemo, they’re, you know, really responsive to endocrine therapy. And other patients have a more fast growing type of ER positive cancer that do require chemotherapy and are almost more triple negative life. And so the idea here is can we use immunotherapy which we know
Works in triple negative breast cancer in this more fast growing type of ER positive cancer. And so the goal here is to see if combining immunotherapy with chemotherapy can improve the rate of PCR. And what that means is if we’re giving chemo before surgery and adding the immune drug before surgery, can PCR
Basically means pathologic complete response where there’s no cancer left at the time of surgery. And so the goal is to try to increase the rates of PCR. And in ER positive cancer, the PCR rates are relatively low, actually. So this type of cancer doesn’t melt away to chemo like triple negative does
The PCR rates and various studies are only zero to 18%. So pretty low. So can we by adding immunotherapy, increase the number of patients where the cancer is gone at the time of surgery. And so this is the study schema. And I’ll know
Actually, the last bullet point is this looking at camera over ER positive cancers was done as part of the eye spy trial, which some of you, you know, may know that or even participated in. And so now it’s a phase two trial. And this is now a phase
Three trials. So taking the early endpoints there that looks promising and studying it in a larger phase three trial. And so this trial enrolled over 1000 patients who had locally confirmed ER positive or two negative grades three cancer, so more proliferative subtype, they had to have at least a two
Centimeter tumor that was node positive or a larger tumor that was node negative. They had to be treated naive, they haven’t yet received surgery, they haven’t yet received any chemo. And patients were randomized to get Pember lism AB, which is one immune drug, in combination with the chemotherapy AC T regimen,
And then go to surgery, or they would get placebo with the AC T regimen. And this was a randomized trial where they’re blinded these patients about placebo versus Cambro. So the patient didn’t know which one they were getting. And they went to surgery. And then after surgery, they would either
Continue the PAM row for six months with endocrine therapy or the placebo with endocrine therapy. And the endpoints for the trial were PCR, so has the cancer shrunk down where there’s nothing left. And then also event free survival, which basically means we’ll follow these patients out over time and
See rates of recurrence. And we don’t yet have the EFF data. But the data I’m gonna show you today is looking at the PRP CR data, which is the earliest data we have for this trial. And what went through that, in the two arms, the median age of patients
Was 49. And each group these patients had, you know, many of them had 63% of them at T one or T two, some of them have slightly larger tumors, about 90% of them had nodal involvement, and most of them had er that was greater than
10%. And here’s the really interesting data. So looking at the primary endpoint of PCR, the turquoise here is the Pember lism AB group and the maroon color is the placebo group. And as you can see, the patients that got Kimbrough had a higher
Rate of PCR. So 24% of patients had no cancer left after the chemo plus Pinborough versus only 15.6% with a placebo alone, the difference of 8.5 percentage points, which is really, really encouraging and the p value is statistically significant. So that was a really exciting new potential to really increase the
Rate of PCR by adding the Pember lism AB. There’s various other definitions of PCR, which I won’t get into for sake of time. But basically, regardless of how you define PCR, we saw about that same margin of benefit with the camera, which is really very
Cool. And then looking across subgroups. You know, this is this line here, zero means they’re equal. And then if it goes further to the right, it favors Pember lism AB if it’s over here, it favors placebo. And you can see that across all
Of these subgroups. These lines are for the most part pushed over to the right some of them crossed the zero for equivalence, but it suggests that regardless of age, PDL one status, etc. How the hell it was dosed most of these favor the
Pember lism AB arm, I think the one I’ll know certainly in node positive patients were further over to the right. In node negative patients there weren’t as many node negative only 65 Here but it does technically cross the zero line there. So I
Think that’s a group of patients where we’ll have to see with more data as it comes out if Kimbro will be beneficial for that group of patients. But really interesting here, that most of these groups did show benefit to come with Pinborough.
For er positivity, most of the patients in the study 601 here had higher than 10%. And those benefited, some of them had a lower er percentage less than 10%. And those patients in particular benefited even more, these patients are more triple negative light. So not tosoh Surprising Things we know that
Pembo works in that group. The question always with any new drug is, you know, what are the side effects? And is it worth it. And as we know, with immunotherapy drugs in general, as we rev up the body’s immune system to help fight cancer,
There’s also a risk of auto immune side effects. Rather than fighting the cancer, the immune system can fight itself and cause things like rash, diarrhea, and then more rarely, things like elevated liver tests. I just mentioned before it’s our thyroid and adrenal insufficiency are also less rare
Than more rare things being hard, long neurologic problems. And so these bar graphs show the rates of these various events with the femoral arm in turquoise and placebo in the maroon and alopecia nausea pretty high and both mostly driven by the chemo. But you can see that some of these other
More rare things, the autoimmune things were slightly higher in the immunotherapy arms. So the liver tests are, you know, slightly higher rates there, for example, diarrhea slightly higher. And then I think I don’t have a slide here, but also slightly higher rates of endocrine toxicities and etc.
Um, so really exciting data. This is the first fully accrued phase three trial high risk early stage ER positive or to negative breast cancer. I think, like I mentioned, the the PCR data is very encouraging that there was an increased rate of
Cancer being gone at the time of surgery. What we really want to know, though, is does that translate into less recurrences. And so what we were eager to see the event free survival data, and that is a primary endpoint of this trial. It takes longer
To get that event free survival data, because we have to wait for recurrences to happen if they do happen. And so we’ll probably end up seeing that data in the next few years. It will take longer, but I think, you know, this probably won’t be
Practice changing, we won’t you know, yet use this drug based on the PCR data alone will really want to see that event free survival data to know if it’s worth adding the pembo. But encouragingly, statistically significant increase in PCR rates by 8.5 percentage points, and PDL one I didn’t show this
Data for sake of time, but PDL one status didn’t matter. So regardless of whether they had this marker or not these all these patients benefited the pet no matter how you define PCR, there was benefit. And then the safety profile with consistent with no known profiles of each management with no new safety
Signals observed. And so at this time point, like I said before, the EFF results are immature. So we need to wait to see what that data looks like to know. But I think a really interesting study and something that, you know, when we finally get the PCR
Data, we’ll know for sure whether it will change practice, but exciting data at this point with the PCR data for now. And then I have a second abstract, Hope Rugo, MD: which I’m just going to bring up a moment and say, just to help people who might not quite get all of those
Details that in PCR, of course is having no invasive cancer at the time of surgery in your breast and node if you’ve got neoadjuvant chemo, and all of these patients got neoadjuvant chemo the standard of care for hormone receptor positive breast cancer where you’re going to give chemotherapy, which is
People who had high risk disease, and they use this great sort of aggressive looking under the microscope and eyes by to which a lot of people know we actually use a gene expression test MammaPrint. And we also look at subtypes of disease where triple negative cancers look more like basal like
Cancers, that wasn’t done. And we hope that that will be done in future studies of of this trial, looking at the tumor tissue that they collected to try and better understand that. And then the second part is to be clear about event free
Survival. So Laura was talking about the fact that PCR is a really important endpoint and we know that if a patient has no invasive cancer at the time of surgery, they have a lower risk of having recurrence than a patient who has a lot of cancer
Left. What’s interesting with Pember lism AB in triple negative disease is patients who got Pinborough even if they had residual disease they had a better outcome than If they did not get Pinborough, which is fascinating. But of course, it’s still better to get a PCR. But this trial only is reporting
PCR, they are not going to have the outcome data for quite some time. And the drug won’t get approved until there’s outcome data. So we won’t be using this yet in terms of our standard of care, but I think it’s really important and interesting. And
Then there was supportive data from a second trial, which I think is really important as well. So just to answer, Amy Nelson’s question, did they stratify PCR by basal like, the tumors that are here are positive and our basal like tend
To have an ER less than 10%. And that represented a very small number of patients in this trial. So that was really important. And it turns out that just looking at high grade tumors was enough to pick tumors that were going to benefit from immunotherapy, which is quite impressive. And the other
Question, which is if there’s no evidence of cancer after these neoadjuvant, treatments, what’s taken out at surgery and you take out the tumor bed, so you leave a clip in there, so you can take out the tumor bed? And of course, one of the questions
And presentation actually at ESMO was, you know, could there be breast cancers where you didn’t need to do surgery. But right now, because we don’t see single cells, we only see, you know, really many 100,000 cells or more. We do surgery, because
We can’t be 100% Sure, there’s not a single cell remaining or a few cells. And we often do even radiation in patients who’ve had a pathologic complete response when they have breast conserving surgery. So this is all upcoming questions that will take us quite some time. So back to you, Laura.
Laura Huppert, MD: Oh, thank you. Great. And then the next trial I wanted to share with you actually is pretty similar. So I think it will help reinforce some of the same points and let me just share that current slide perfect. So this trial is also a
Phase three trial looking at immunotherapy in the same patient relatively similar patient population high risk ER positive her to negative early stage breast cancer, rather than using Pember lism AB which is one PD one inhibitors. This trial looked at the use of Nivola Mab which the different
PD one inhibitor. And so like we went over before the most common subtype of breast cancer, you know, rates of PCR are low, can we basically improve those by adding immunotherapy. So same kind of rationale here. And this is a study designed for this
Trial. So very similar inclusion criteria in this trial to the other trial. So newly diagnosed ER positive or two negative patients. The slight difference here is t one C and T two could be no negative in this group, whereas the other trial that had to be noted positive, so slightly lower, but there
Weren’t actually that many of those patients. The other slight differences, you remember the last trial, they all had to be grade three. So this trial was grade two or three, although actually the majority of patients ended up being in grade three, adequate organ function, good performance status. And so
These patients that met criteria with these high risk ER positive cancers were again randomized. Similarly, one to one, half of them got nivolumab with the AC T chemotherapy, and the other half of them got placebo with AC T chemotherapy. So very similar, you know, strategy here, went to surgery and then continue the
Nivolumab or continued the placebo, with an endocrine therapy as well afterwards. This trial was powered for PCR only. They were they there were various issues with the trial, which I won’t get into where they ended up not powering it to look at EMFs event free survival, like the other trial.
So it’s not technically powered for that it was just powered for PCR. But nonetheless, they’ll certainly follow these patients out to look at events over time there. These are the patients they’ve all been treated at this point, about half of them had
Completed therapy at the time of being reported. And some of them were still on study. So just like the last trial, this was an early look at this, this data. And these are the PCR results for this trial. So in this trial, 13.8% of patients who got
The chemotherapy alone that UCT achieved a PCR versus 24.5%, who had the nivolumab added a difference of 10.5%, which was statistically significant. So pretty similar numbers actually to the other trial, right? You’ll remember the other trial, the difference was 8.5%. But pretty similar numbers have
Pretty similar margin, which is reassuring actually, that both trial saw a relatively similar benefit and indeed saw benefit here in terms of PCR with the addition of the immunotherapy and the PDL one they look det does PDL one status matter? I
Didn’t show this data on the last one. But we look at this marker of PDL. One is basically house it the marker of immunotherapy sensitivity. And we know that patients who have higher Pdl, one tend to respond better to immunotherapy. So as
You can see here, these patients who had Pdl, one that was greater than or equal to 1%, had an even higher rate of PCR and an even bigger difference 20.2 versus 44.3, the 24% difference, versus those that were PDL one less than one, they did still
Did have benefit here with a nivolumab. But only a 3.6% benefit there. So interesting to note that, um, and secondary endpoints. So in addition to looking at PCR, the PC, the definition of PCR, like I mentioned, is no cancer left at all in the breast in the lymph nodes. In addition to just
That’s a binary thing, right, either you have no nothing left, or you do have something left. We also have this categorization called RCB. And that actually stratified if you do have cancer left, is it just a little bit left is it a moderate amount
Left or is a lot left and so RCV one is just a little bit left, two is more three. And so they also looked at rates of RCV zero is essentially a PCR or DD one is just a little bit left. And
So when they combine these two RCB, zero and RCB, one, they saw 21% rate in the chemo only group versus a 30.7, a difference of 9.1%. So also reassuring as there as well. And similarly, looking at the pupae, PDL one status, a much more dramatic
Difference in the PDL one positive patients on the actually technically didn’t see a difference here in the PDL one negative patients when they combined RCV zero and one. Sorry, I don’t know why these slides a draft finalized, you can ignore that this is the final presentation there. But in
Terms of safety data here, like I mentioned, the rates of adverse events, some of them are related to chemo. And what we care in particular about is the rates of autoimmune side effects. And so I think there’s a separate slide. Here we go. So skin and thoughts on having skin disorders related to
Immunotherapy is relatively common gi toxicities, endocrine toxicities, and I don’t have this particular slide showing the specifics but slightly higher rates of autoimmune effects. And so to summarize this data, there was an improvement in PCR of difference of 10.5%. Also an improvement RCV. The benefit was more pronounced in patients who had a
High PDL one score, and then the safety profile was consistent with known profiles, we know that immunotherapy can cause these auto immune side effects. And so that’s something that we’ll watch for rates of those long term for these patients as well. So I think to summarize both of these trials, we saw a
Benefit with the addition of these Pdl, PD one inhibitors in both of these trials, I think we’ll need to see whether this translates into reduction of recurrence risk long term. And these won’t be approved yet until we see that data. So I think we’re eager to see that data, hopefully in the next
Couple of years to know if it’s something that will ultimately use for patients like this. Hope Rugo, MD: Yeah, I think it’s fascinating and also really exciting for us that this all came out of, really our work. And I Spy where we looked at more detailed, and I think,
Probably better assessment of which patients might benefit or not. So we’re looking to the next year and seeing if the further analysis of the tumor samples taken from diagnosis from the patients on these trials might give us more information about the subtypes and who benefited and if there’s
More data, the trouble is, a lot of these large trials that are, you know, so called registration meaning for approval of drugs, they don’t, they don’t have a lot of tissue collected. So we’ll see what we learn because we also don’t want to be just
Giving, you know, immunotherapy to everybody, and then they get the side effects which they want them to need, you know, so that’s an important thing. Laura, question from one of the people was what is the reason that only her two negative patients were part of the trials because there’s already an
Effective treatment, Herceptin for her to positive tumors? Yeah, Laura Huppert, MD: good question. We do have Yeah, Herceptin and Perjeta. And other her two targeted agents for her to positive. There are separate trials looking at the use of immunotherapy in her two positive patients as well. And
So that data sound that will be presented next week at San Antonio actually, but these trials in particular focused on the her to negative population. Hope Rugo, MD: Great, excellent question. And then for those of you are putting some questions in the chat, we are going to
Talk about metastatic breast cancer next, and hormone therapy we’ll talk about after the trials that Psy is going to talk about now, which is some antibody drug conjugate data. But we then will talk about these other questions that are coming up in our q&a. So stay tuned, we’ll be there. All
Right, so I is going to talk a little bit about some antibody drug conjugate data. Saya Jacob, MD: Okay, just share my screen. All right, so the first abstract we’re going to talk about today is looking at truss tuza map directs Tekin t dx d for short.
Some of you may already know of this drug, but it goes by the brand name in her to basically, as Dr. Rico mentioned, this is an antibody drug conjugate what that means is that one side of the drug binds to an antibody and exactly what antibody it
Binds to is different based on the drug, and the other side has a payload or has a chemotherapy. And so the idea is that by using these antibody drug conjugates, we more in a more targeted manner, deliver the chemotherapy to cancer cells. So this
Particular antibody drug conjugate t dx d are in her two binds to the her tube, protein and has a payload again, that’s a chemotherapy payload. It’s actually already FDA approved based on the results of this trial, that destiny breast Oh, four trial. And this abstract actually gives more updated data
With long term longer term follow up. And so we really need to see how these drugs perform over time to really understand the benefit to patients. So by way of a little bit of background, many of you know that breast cancers actually expressed a variety of different receptors on their surface, we
Talked just a little bit about hormone positive breast cancers that express estrogen receptor and progesterone receptor, and then a little bit about her two positive cancers that have increased levels or amplify levels of the herd to protein, there is a subset of patients that don’t technically meet
Criteria for her to positive, they don’t have enough expression, enough amplification to really get that designation. But they do have low lying levels of her to expression. So when we stain it, we see that there’s some expression of the her to protein, but just not enough to classify them as her
To positive. And so the idea behind this trial was in these patients, if we use this antibody drug conjugate directed against the her to protein, and we still see a benefit. And so that was the initial Destiny breast O for analysis. And it showed an improvement in progression free survival,
Meaning the amount of time that patients were on the drug before they needed to change, and then overall survival as well. And so this, so the primary analysis was a follow up of 18.4 months. And so this updated analysis is even more follow up data. The
Way this trial worked his patients who had her to low meaning low levels of the her to expression, but not enough for her to positive and had metastatic breast cancer, and that already undergone either one or two lines of chemotherapy, they were randomized either to receiving t
Dx d, or to getting chemotherapy kind of standard chemotherapy regimens that would have been available to them otherwise. And so this is the overall survival both with the initial analysis as well as the updated analysis. Dr. Hubbard went a little bit into how to look at these curves. But essentially, the
Higher up you are, the better survival you have. So that blue line there, that’s the those are the patients that got t dx d, and you can see it’s higher than the gray line. Those are the patients that got chemotherapy, meaning that those patients actually had better survival, you’ll see that there’s two
Survival graphs on this slide. On the left side, it’s for those patients that are hormone receptor positive, so they have low levels of her to expression and they’re also hormone receptor positive, and they had a survival benefit. On the right, it’s for all patients, so they could have been hormone
Receptor positive or negative. And again, you see that there’s a survival benefit with using using TD XD over the standard chemotherapy agents. This slide shows the overall survival and progression free survival of patients with hormone receptor negative patients. So remember, all of these patients still had
Her to low disease, low levels of that her to protein, but they may have had estrogen receptor and progesterone receptor, either positive or negative. And this is the group that’s negative. And you can see even in this group that the TD XD patients that’s that blue line, did better and had better
Overall survival compared to the patients that had standard chemotherapy. The one caveat that I will say about this is there’s only 40 patients in this trial that are being analyzed that have hormone receptor negative disease and in other words that these are 40 Patients who have triple negative disease
Versus when you look at the hormone receptor positive cohort, the numbers are closer to 330. So there’s a big difference in the number of patients in the subsets. But even with that difference, we still saw that there was a benefit for the hormone receptor negative patients. And there
Were a variety of different subgroup analyses done to see if there’s certain subgroups of patients that benefit more from PDX D, compared to chemotherapy. So they looked at patients who had prior CDK, four, six inhibitors. So these would be drugs like ribociclib, or kisqali of MSI, glib or zeneo,
Or palbociclib, or I’ve Rance, and it looked like regardless, there was still a benefit for TD XD, they also looked at the benefit based on the amount of the her to expression. Remember, they all had low levels, but some had very low, some had more
Moderate. And still there was a benefit. And actually, for most of the subgroups, we saw that there was still a benefit for giving t dx d over other chemotherapy. And of course, it’s important to think about toxicity just because the treatment is improving survival. If it’s causing a lot of
Toxicity, then that’s not necessarily helpful. And so when they look at t dx d, one of the major side effects that cause treatment discontinuation was ILD or pneumonitis. Another way, in other words, inflammation of the lungs related to the drug, and that happened in about 10% of patients. So still not a
Majority, but definitely a sizable minority and something that we always have to keep an eye out for when patients are on TD x d. And then other side effects that we’re seeing were nausea. That was about 4.6% of patients that had nausea bad enough that they needed to reduce the dose, and decreased
Platelet counts as well. And so with the longer follow up, we really saw that that that the survival benefit with TD exe that we saw initially with the shorter follow up really stayed true, even when we follow patients out for a longer period
Of time. And we also saw that the safety profile was similar to what we had already seen, namely, that we need to watch out for lung inflammation or ILD pneumonitis watch out for nausea and watch out for lower blood counts. But overall, I think
This is a really incredible and amazing new option for patients who have heard too low breast cancer have already undergone one or two lines of chemotherapy that this can really be a beneficial option. Hope Rugo, MD: Yeah, that was really helpful and interesting.
I think the you know, outcome with 32 months was almost identical to the earlier outcome, although now investigator assessment says so that’s really great. And I think that the, you know, that was very encouraging is there is an ongoing study using t dx d, which is also known as inherent
To, but we’d like abbreviations and oncology. So this drug is also being tested in the first line setting. So after you’ve gotten hormone therapy and targeted agents and need to move on to chemotherapy, as a first chemotherapy option compared to standard chemo, and they’re including patients who have very
Little her too, so, so called Ultra Low, not zero, but closer to zero than one plus. So that’s a whole complicated area. We’ll see what happens with those results next year. But, you know, I think what’s been astonishing for us in oncology
Is that you could use an antibody targeted to her to this is citrus tuza, map biosimilar, and attach a toxin to it and use the right linker, and have this efficacy in tumors that are, by definition her too negative. And they just have a little
Expression of her too. They didn’t realize those patients did not have a response to an earlier antibody drug conjugate called Cat sila. And they never respond to trustees a map and produce a map either. So Herceptin and Perjeta. So it’s really quite interesting and really remarkable data. And of
Course, there’s interest in moving these drugs to earlier stage treatment as well. Although there is alternative drug that AstraZeneca that is partnering with he on this drug, probably will move forward with and is already moving forward within the earlier stage setting to we have a second antibody
Drug conjugate that’s approved, SS G’s map COVID T can and that one we call sassy, also known as tro del V, and that one is, regardless of her two status all her to negative again, and is approved in patients who’ve received two lines of systemic
Therapy for metastatic disease. The difference is that there’s different side effects from these different drugs. So choosing the sequencing of treatment is a big challenge for us. And actually, Laura will has done a project on this along with others, and they will be presented at a discussion
Session at San Antonio, talking about what we know now about sequencing, different antibody drug conjugates and how we can improve how we understand this effectiveness moving forward. So really an exciting area. So this other antibody drug conjugate was presented, which site we’ll talk about, but I just want to
Answer one question by Kelly Shanahan about the recommendations of frequency to chest screening will decrease the risk of death, which was 1.1% in Destiny breast, oh four from interstitial lung disease. And I do think that getting CT scans every six to nine weeks in the first year since 87% of the
Pneumonitis occurs for the first time in the first year. That if we do the CT scans and hold drug if we see inflammation without symptoms and treat with steroids, and discontinue drug, discontinued drugs, permanently if patients have symptoms of shortness of breath or cough, with those CT chest CT findings
That we can potentially completely avoid mortality from these this drug. So I do think the screening is making a really big difference. So tell us a little bit about data Poteau Mab directs to can well do okay, Unknown: let me share this one.
Saya Jacob, MD: Okay, so this abstract is looking at data poda map Dericks T Kennedy. So this again is another antibody drug conjugate. Remember antibody drug conjugates. On one side, bind an antibody and on the other side deliver a payload or chemotherapy. This one in particular is different from the
One we just talked about in her two, but similar to the one that Dr. rugo just mentioned, Sasa twosome AB and that it binds a similar antibody that trope to antibody and again delivered chemotherapy agent. And so this drug was used in patients who had metastatic hormone receptor positive and her to negative
Breast cancer. And so this kind of just talks about how these antibody drug conjugates are made that they have one side again, that’s directed against the antibody, in this case, the trope two. And then the other side that has some kind of toxin. In this case, it’s a topoisomerase, one inhibitor,
Basically a chemotherapy agent. And so in this trial patients again, who had metastatic hormone receptor positive breast cancer, who had already undergone one to two lines of chemotherapy, and also progressed on endocrine therapy, were randomized either receiving data poda Mab dx d, or getting chemotherapy kind of standard chemotherapy regiments. And so
This tells you a little bit about the two different groups. I think the main takeaway here is that between the two groups, patients were overall pretty similar age was similar. The numbers were similar 360 and each group racial and ethnic breakdowns were similar number of patients that got one versus
Two lines of chemotherapy or got prior CDK four, six inhibitors. Were all kind of similar same with patients that have gotten prior taxane or anthracycline, which is important when you compare groups to make sure that they are somewhat similar in who’s being enrolled in the groups. And so this is the
Progression free survival. Remember, progression free survival means the amount of time patients can be on a treatment before they need to switch, typically for progression or sometimes for toxicity. And again, the higher up on the y axis the line is the better survival there is. And so
You can see here that patients who got the dado dx d are represented in that purplish color compared to I guess they’re both kind of purple with the darker purple versus the more indigo color. So they had better survival compared to patients getting standard of care, chemotherapy, and the
Toxicity from this trial. So I think this is a really important takeaway that the grade three toxicities, meaning toxicities that we consider to be severe, were a lot lower in the patients who got the data of dx d. So it was 75 or 21%, compared to 157,
Or 45%, getting standard chemotherapy, which is a really so really important not only does it seem to improve progression free survival, but it’s also better tolerated by most patients. And that’s, I think, really, really important. The most common side effects that we’re seeing were low blood
Counts, especially anemia or low red blood cell counts and neutropenia, or low white blood cell counts, and so patients may have needed shots, growth factor shots to help increase white blood cells. Some patients also developed dry eyes, and then there were a variety of GI symptoms like nausea vomiting,
Constipation. stomatitis is another way of saying mouth sores, fatigue and then hair loss was seen. And so overall, there was improved progression free survival with the use of dado DX DEA again, this is for patients with stage four metastatic hormone receptor positive cancer who’ve already
Undergone endocrine therapy and one to two lines of chemotherapy and for these patients dado dxc, may be really beneficial. We have at this point seen a progression free survival difference, what we really need longer follow up to determine if there’s an overall survival difference are patients on dado
Dx d actually living longer to really make that full assessment. I didn’t go through this data, but there was also a higher objective response rate in the patients that got dado dx d compared to chemotherapy. Basically what that means is that when we look at the scans that there are patients who have
Clearly less disease burden on the scan. So another really promising sign that this is a really helpful antibody drug conjugates. We talked a little bit about the really, incredibly, the incredible difference in the toxicity that’s seen thus far. And the decrease in grade three toxicities or severe toxicities with ADHD as compared to
Standard of care chemotherapy, and that most toxicities that were experienced were actually lower grade toxicities or milder toxicities. And so I think this is an exciting new antibody drug conjugate. The data is still preliminary but very, very favorable and I think will be interesting to see with longer follow up what we find.
Hope Rugo, MD: Yeah, I think this is really interesting and certainly encouraging. We did actually looked at data dx d in our eyes by trial. And that was, you know, we, we don’t have a report of that data yet the arms have closed and it one arm was
Data with just itself for for two doses and the other is neoadjuvant therapy. The other was data dx d with an immunotherapy drug from AstraZeneca durvalumab. And for four doses, and then, you know, we base our assessment with MRI and biopsies on response and what happens next. So it will be
Fascinating to see that data next year come together to understand how those drugs worked. And, of course, this drug is being studied in triple negative breast cancer, both in metastatic disease and in patients with residual cancer after neoadjuvant therapy. So also is the antibody drug
Conjugate tro del v or Sesa T’s mouth COVID T can with Pember lism AB the immunotherapy drug, and then data Poteau Mab will be given before surgery in more doses and another type of study. So these are all very interesting. And of course, the drug we talked about earlier trustees mapped directly to
Canada’s approved for her to positive disease, where it is dramatically better than our standard antibody drug conjugate huge impact. And so that, you know, it’s clearly big, big impact there. So. And so I think one of the questions, some of the questions here are a little bit difficult to just there.
Kelly asks, Is there data on differences between truth to expression and the there that analysis has not yet been presented for you data Pro to map drugs to Ken entropion. But I think that we will see data in the very near future about that. Because there’s additional data being presented at San Antonio
And of course next year. And then one of the questions is, if the drug is approved, where we you choose after progression on CDK, four, six inhibitor, and I think there is a balance of toxicity. That’s probably a little bit too much detail to go
Through here. But I think we’re also waiting for the survival data from data promap. So that will play a role. What do you think so? Saya Jacob, MD: Yeah, I agree. I think it’s, it’s really good that we’re seeing the PFS benefit, but we really need to
Wait for that overall survival. I think before choosing it over other things that have a demonstrated overall survival benefit like Sasa tuza map Richard ellaby Hope Rugo, MD: and I buy was one of the questions was your low positive included in this study? Saya Jacob, MD: I think I have to say
Hope Rugo, MD: did one for anything great 1% or greater, was included? I don’t think there were tons and tons of patients who were low, but we don’t even have that data yet. It will come up later. And I think that you know, looking at
Is this by er differential, the estrogen receptor, how positive it is, will be really interesting to see. But again, this is very new data. And we’ll see more of that as we go forward. And, you know, because data dx d works in triple negative disease like societies and networks or Delphi, it won’t
Shouldn’t really matter whether the tumors are low or not. And then also, you know, that it’s really hard to keep biopsy tumors as patients know when you keep poking needles in patients and not getting enough tumor. And so, you know, we don’t actually know if the ER is maintained when patients Started
On study because even if they had ER positive disease when they got diagnosed, the ER goes away in some tumor. So that wasn’t an analyzed carefully with any of these studies because of course they efficacy crosses ear. So Laura, question from the let’s see answer live got that cancer from a question
From the q&a is, is it a good idea to use zo together with kisqali Every month during the rest of weeks for years, Zo being the growth factor filgrastim. Some people also use it, that’s a biosimilar. It’s also called Neupogen and kisqali ribociclib, one of the CDK, four, six inhibitors. Yeah,
Laura Huppert, MD: so um, I don’t, we don’t generally use our zeal in this setting. So kisqali ribociclib, is given three weeks on one week off, so that you’re the during the three weeks on your white blood cell goes down, and then the off week
Allows it to recover. And we usually don’t use RZ, we just allow that time to allow for recovery. If it’s still low after the seven days, there’s a few options, I think one option that I use commonly is add a few extra off days. Or the other
Thing you can do is lower the dose of the ribociclib rather than using Zarxio in this setting. Yeah, Hope Rugo, MD: and I think that’s a really important point because xar ribociclib, in the metastatic setting is given initially, it’s 600 milligrams. But when patients needed to dose
Reduce, most commonly for neutropenia, sometimes for liver enzyme abnormalities, which can be seen, then they got 400 milligrams, they had the same outcome. So the same benefit from ribociclib, as if they took 600 milligrams, and that actually led to 400 milligrams being the dosage that was used
In the early stage study called the Natalie trial. So we don’t use growth factor, the only setting to use a growth factor shots, so called Zarxio. Here in this question, is in patients who have fever and low neutrophils, so a serious infection, otherwise, people don’t seem to get serious
Infections, we just follow and wait for recovery. And if recovery happens in 10 days or so we’re good. And if it really keeps being really low and below 500 Is the neutrophils then we dose reduce. So but we don’t give xarvio. And the question
Was, Is it a good idea? Because it’s not needed? It’s not a worthwhile use of expense and poking you. It doesn’t seem to have a downside. Except for that there’s no upside, so I wouldn’t use it. Another question that comes up is, if the ER goes
Away, is the patient or their tumor triple negative side? Is that the case? Saya Jacob, MD: Yeah, I think we see this often as people get treated with hormone agents that the cancer sort of changes its expression. But I don’t necessarily think that we would
Think of it as triple negative, it’s still has a biology that seems more akin to hormone receptor positive disease, but it may indicate that the tumor is less responsive to more hormone agents and mean, we may need to change treatment to more chemotherapy based agents. The other thing that can happen is
Sometimes the treatment itself can cause decreased levels of er expression. So for example, with fulvestrant, or Faslodex, oftentimes, we see that if we biopsy after giving that, that the tumors don’t necessarily express estrogen receptor, that doesn’t mean that they’re not hormone receptor positive
Cancers, it’s just a function of the treatment that we’re giving. Hope Rugo, MD: Yeah, it’s a really good answer. And I think that we for the purposes of these trials, when a patient if a patient was had ear positive disease, and then their biopsy
Shows ER negative p or negative energy negative disease, they would be classified as triple negative for the purposes of clinical trials. I think the caveats in addition to what Simon mentioned is that if you biopsy bone and decalcify it you can lose er, so that can give you a false negative. In other
Words, you really do have hormone receptor positive disease, but The biopsy says it’s ER negative. And we’ve had people respond to hormone therapy for years who had a bone biopsy showing it was here negative. So one has to be very cautious in that situation. But we do see loss of er in patients
Over the course of years and with more aggressive cancers. And then Kelly also points out in our q&a box that if you’re Neutrophils are low in the morning, like if you do a first blood draw first thing in the morning, and you’re on one of
These CDK, four, six inhibitors, and it’s your week off and you’re doing your test. We found that people it’s so funny because we only learned this through the CDK for six inhibitors. People’s neutrophils could be low, but they that’s because they all stick to the walls of the blood vessel
Overnight. And if you run around, we don’t know how much running around you. It’s not very scientific, but if you run around and run upstairs, move around, check your labs a little bit later. or it can go up. And sometimes we see people double
Their neutrophil count just by moving around a little bit and waiting a couple of hours. So it’s just a lesson not to do the labs very first thing in the morning because you’re likely to be low even when you might not be. So then that will make
People nervous, you know about that. Another question that is in the q&a is what is coming up for patients who have ESR one mutations. And, of course, there’s a lot of interest in new agents for ESR one mutations, and we have one drug that’s
Approved LSS. Trent, do you want to talk a little bit to that, Laura? Laura Huppert, MD: Sure, yeah. So um, an ESR. One mutation is a specific mutation in the estrogen receptor that makes the tumor more susceptible to certain mutations called oral surds. And there’s one oral sir, that’s currently approved,
Called LSS Stryn, based on a phase three trial called the Emerald trial that compared this to fulvestrant, which is a shot form of assert. And so these are basically oral forms of the same drug and showed that it was superior. There’s a number of different oral surgeons under investigation right now. And a
Lot of interest in can be combined these oral surgeons with other agents as well. So combining them with like a CDK, four, six inhibitor, or, you know, other, non other other agents in general. And so, hopefully, we’ll get some of these combinations approved in the future as well. But I think
It’s a good option. And the question always is like, When should I test for these Yes, or one mutations. And the important to understand, yes, there are mutations develop in response to endocrine therapy. So while you’re on an AI and your first line, it’s not worth checking it at the beginning, because you’ve
Probably won’t have it. But as you’re on the AI for a longer time, and then your cancer grows, that’s when you want to check it as at before you start your second line is check it at that point, because you might have developed in the interim,
And if it has developed, then you would be eligible for some of these therapies. And so important to understand that you can kind of repeat this check over time to see if that mutation develops, and if it’s an option for you. Hope Rugo, MD: I think that’s a really nice explanation of this.
I think the issue with these drugs is that, you know, when a new drug comes out, there’s always a lot of interest in trying it. But the LSS Trent data suggests that the responses are better if the cancer is still sensitive to endocrine
Therapy. So as a million line option, after lots of chemo, it’s really unlikely to work, it’s going to work more in patients who still have hormone sensitive disease. And usually that one of the things they looked at in the Emerald trial as a surrogate marker of hormone sensitivity was how long a
Patient had been on a CDK, four, six inhibitor, and patients who had been on for 12 months or longer seem to gain a really big benefit from taking LSS Tran versus standard endocrine therapy, which wasn’t the same as their other drugs. And it’s specifically in that ASR one mutate mutated group, so that
Where the tumors got ESR, one mutations were, the benefit was seen. Now the newer endocrine therapies that are being studied, there are some that have been suggested to work better, even regardless of ESR. One mutations, they degrade the estrogen receptor and downregulated. There are some
That prevent the formation of the estrogen receptor through a complicated process. You know, it’s going to be interesting to see what happens. And the but these drugs seem to be very potent and reasonably well tolerated. You know, some funny little side effects, but we don’t know how big they are
Until we get the big randomized trials, because these are all very early. And they’re all which is great. So I think the big question for us now is, can we combine them well with our other targeted agents and move them forward? In patients who
Have, you know, tumors with the SR one mutations without it’s kind of hard to know, I mean, assessment had a hint of activity in those patients who didn’t have ES or one mutation. So I think that it’s very possible that we’re going to
Have a lot of these drugs in the future that will really give lots of new outcome, not lots of new options. And then of course, if that happens, the next interest is seeing if you could replace an aromatase inhibitor like so you gave a patient and
Aromatase inhibitor for a higher risk cancer, early stage disease. And after there’s a trial we have opened at UCSF where after two to five years of that aromatase inhibitor you can be randomized to either switch to the oral surd drug called inland restaurant or stay on your aromatase inhibitor. And I
Think that that’s a very cool trial because you have a 50% chance of getting the new drug. And if you don’t get the new drug, you’re still getting standard therapy with close follow up. So, to me, that’s, I think, a really exciting new approach in patients who have already been on aromatase
Inhibitor. We have a bunch of trials open in the metastatic setting in our Very excited about seeing how these move forward. Most of them have combinations with various drugs. So that’s exciting. Now what happens if you have an ASR one mutation and you don’t have a lot of drug options? I think,
Obviously, the antibody drug conjugates are good options. There are other targeted therapies and earlier stage studies as well, that may be options for patients. So, let’s see, then there’s another question, which is interesting. Do we think that combination therapies will be better than mono therapy in patients whose cancers start growing on
Endocrine therapy and a CDK, four, six inhibitor in the metastatic setting? So I don’t know what do you think, Laura, about that? Yeah, Laura Huppert, MD: I’m hopeful that the combinations will be even more effective than the mono therapy, I think we have to
Wait of course and see the data. Like hope was mentioning, those patients that had a long duration of response greater than 12 months on first line, tend to do better, but those who had shorter progress more quickly on the LSST. And so in
Particular, those patients that don’t have as long of a time on first line, I think combination will be a key to try to maximize benefits in second blinds and beyond. So I am excited to see some of that data coming out soon.
Hope Rugo, MD: Yeah, I think that that’s a really good point. And I do think that we’re excited about combinations. In fact, one combination that we studied with a drug called copy of assertive, which is called an AK T inhibitor, and it inhibits
Part of a pathway. That’s the most commonly altered pathway in breast cancer called the PI three kinase pathway. And that drug combined with fulvestrant, Faslodex, improved progression free survival, and was recently approved aside you went tell us a little bit about that, and the side effects of computer sensitive. Yeah,
Saya Jacob, MD: so as you mentioned, it’s targeting a mutation that’s found in many breast cancers. And this can be tested, sometimes by doing CT DNA testing in the blood to look for the aka T mutation or from tumor biopsies. Of course, as we
Mentioned, that’s a lot harder to do repeatedly. And so for patients who have who do have mutations in the AK T, and have already received CDK, four six inhibitors and progressed on that this drug Captiva sir tip has just recently been approved.
And it’s been shown to be very effective. As far as the side effects, the most common things seen were rash and diarrhea. In the computer, sir tip group in this was in a trial where it was combined with fulvestrant. So potentially, there’s some interaction there, but Jeff, predominantly rash and diarrhea
Were what was seen. Hope Rugo, MD: Yeah, I think that rash was seen about 38% and diarrhea, series area and about 10%. Um, it’s kind of interesting. I mean, TD XD, we heard about, you know, 78% of people get nausea, although only a small percentage get bad
Nausea, and we can control it pretty well. We don’t see a lot of nausea with these drugs. But we see other toxicities and when you affect the PI three kinase pathway, you do get rash and diarrhea. But thankfully, you don’t get the sugar problem so
Much that we see with the other drug that’s approved here called El Pellissippi. Pick array, where the sugar problems were really a huge challenge to deal with. So and rash seems to be more common and more difficult to manage copy, copy of
Assertive or true cup is given for four days on three days off. So it probably helps with the management of the side effects. And we’re studying actually the previous narrative in combination with a CDK, four, six inhibitor and endocrine therapy fulvestrant in patients whose cancers recur early on
Their early stage treatment to see whether because in animals, that triplet worked really, really well. So we’re trying to see if that happens, it seems like it’s an effective combination. Is it better than giving to drugs? That’s what we need to answer the question about. And so then, let’s see,
We answered those questions. And of course, put your questions in. I mean, if we didn’t answer them or anything else, I think what I’ll do is just so somebody asked about the key 67 requirements for the monarch e trial, and the monarchy trial
Was actually updated at ESMO. If I can find where I what I did with the slides here. Okay, there it is. And I’ll just show these quickly, because I think it’s worthwhile just seeing this. I mean, the reason why this is exciting for us is that
The, you know, we want to be able to reduce the chance of distant recurrence in anybody who has early stage hormone receptor positive breast cancer, as much as possible. And since the CDK, four, six inhibitors are pretty well tolerated. And you could, you know, improve survival in metastatic disease.
The idea was that maybe if you gave it an early stage high risk disease, you could also improve outcome. And we’ve seen some very cool things with this study, actually, so let’s see if I can get to my button to make it into a full screen. Okay, so
This was the update here, and we participate in the study. So that’s why we’re also authors on this. Let’s see. And this is the studies the monarchy’s study randomized patients who had no deposit or high risk early stage breast cancer. And they had to
Have a high risk based on having one to three positive nodes and grades three disease or a tumor greater than five centimeters, or a Ki 67, a marker of cell turnover that was 20% or greater. And then if you just had four or more positive nodes,
You were eligible patients all got their standard hormone therapy, and then they were randomized 5600 women to receive abemaciclib Or not Vemma. Cyclic is also known as vers Ennio, and it’s taken twice a day continuously. So it doesn’t get that week off, like ribociclib and palbociclib. And they did an
Analysis. Now, this is their third interim analysis, basically looking to see what happened, you give the abemaciclib for two years. And then you continue the endocrine therapy for as long as the doctor thought that patients should stay on it, and look to see whether or not patients have
Recurrence or not. So remember that now patients, the median is five years of follow up out here. So people have been off treatment for a median of three years with abemaciclib, although they’re still taking the hormone therapy, and then the control group just was on hormone therapy the whole time. So what
They saw, which was really fascinating was that patients, here’s the abemaciclib period for two years, that if you go out to 60 months, this now five years, that the curves are still separating more and more. So there’s less and less recurrence, the further out you go, which suggests that just
That two years is still impacting these recurrences that occur three years later, which is amazing. So from 2.8 4.86 7.6%. So really exciting to see that continuous benefit. This just says that all the different subgroups of patients benefited. And then what’s really important, I
Think, to the patients and to us, as oncologist is preventing distant recurrence. And you can see that you’re also seeing this continuous improvement in the benefit of adding abemaciclib to endocrine therapy out to five years with now the difference being almost 7%. So it does suggest that when you do this
Treatment for two years that you’re getting this sort of long term effect, which is amazing. And there were although survival is still early, and this is actually a really good thing for our patients that survival for early stage, hormone receptor positive breast cancer, even with recurrences improving
Continuously with our better therapies. So that’s great, because these curves are still very, very good at five years, even with high risk cancer. But there were actually less numeric deaths. So 234 versus 208. And there were less patients who actually live were living with metastatic disease who got
Abemaciclib. So it seems to really have reduced that this is the green living with metastatic disease. Here’s the abemaciclib Here’s the ones who took endocrine therapy alone. And then in terms of the question that was in the chat about Ki 67, this is a marker of proliferation, and originally
The FDA, in an abundance of caution, the drug causes diarrhea, and it’s expensive, and you have to take it for two years, and it causes fatigue, right. So and people have largely finished their chemotherapy, surgery, radiation, and now they’re taking an addition to endocrine
Therapy and other agent. So they said, well, Ki 67, you know, as a high risk, a prognostic factor, so they can just approve it in the Heike 67 group. But then with this longer term follow up that happened regardless of key 67. They took
Away that requirement earlier this year, which was late I mean, we already were just not using it in clinic fixed didn’t make any sense. But here you can see for invasive disease free survival. So that’s any kind of recurrence distant recurrences. These hazard ratios which show the relative benefits are
Identical regardless of whether you add a low key 67 or Heike 67. So I think that that’s really convincing for the fact that the drug works regardless of Ki 67. I will say that the patients who had very high ki 67 had a higher risk of recurrence.
And with endocrine therapy, had the highest risk of recurrence here, as you can see that 25% At some distant event by five years, so we definitely want to improve that outcome. And this is a really big improvement in outcome here. And safety. Basically, there was no new safety events because everybody
Was off treatment, but abemaciclib causes diarrhea, some little increase in liver enzymes. If you take it with tamoxifen, can increase blood clots. And then it can also cause low neutrophils, but it’s just much less common than ribociclib or palbociclib. So that’s great. There was no long
Term effects, which was very exciting about this. So I think this was a very exciting ongoing data. And it was the data, the first data for years that continued to show the kid this carryover effect that led to the FDA, dropping the Ki 67
Requirements. So that was very exciting. So, and one of the questions is, why does it still work after two years? Do one of you want to tackle that question? Saya Jacob, MD: I can say that I’m not sure. And I don’t know
That many of us are really that Sure. It might be something to do with the latency of any cells that might still be within the body. And somehow the CDK, four, six inhibitors are able to target those cells. But, Laura, I don’t know if you think
Laura Huppert, MD: I’m referring to the carryover effect that hope was mentioning the fact that even if you’ve only been on it for two years, if you are able to kill more of those cells, the benefit is still there beyond those two years. And so you’re seeing less recurrences even further out.
And so the curves get wider, because you’ve kind of done that work in those first two years and carry over to have that benefit going forward. Hope Rugo, MD: Yeah, I would agree with that. And I think that one of the thing that’s poorly, very poorly understood
In ER positive disease is this concept of dormancy, that you have cancer cells that are alive that are destined to grow back and cause recurrences, and we see these late recurrences, you know, 1015 years out, and even further. So this idea is that you’re killing those dormant cells early on, even though
They’re not cycling very much. So I think that’s really exciting concept. We had seen it with hormone therapy. So if you gave five years of tamoxifen, you still were having a better impact on recurrence at 15 years compared to giving two years of
Tamoxifen. And this was a study which has, you know, done a very, very long time ago. So really interesting. One of the questions also came up is why not get five years like the hormone therapy. And, in fact, ribociclib, or kisqali, tried to address this in the Natalie trial, where they gave three
Years of ribociclib. They just have presented data where only a small percentage of people have finished three years, but have already seen an early improvement that significant and invasive disease free survival and distant recurrence. So we’ll see an update at San Antonio on that. And we’ll continue to see
Updated data, it’s still early, but they gave three years. And you know, of course, we’re not comparing three years to two years. So we’re not gonna even know what the right number is. And they treated patients who were a little lower in terms of
Risks of some node negative patients who weren’t included in monarchy. And then of course, there’s a related question, which is that why in the patient forums and online groups are oncologists using three years of Virginio instead of two or abemaciclib. And that’s really just because of the Natalie
Trial, we have no data to support it. It’s kind of a funny thing, actually, that people are doing that. But you know, you get anxious when somebody has a lot of positive nodes. And you know, you really want to improve outcome, it’s very hard to stop.
And that’s kind of situation where you’re feeling particularly concerned about risk. So, we have gone through most of our presentations, we have a little update on the Neo adjuvant immunotherapy trial called Kino five to two, but that’s going to be updated further next week. So I figure
We’ll just talk about it in January when we do San Antonio, there were a lot of really interesting small bits of data, talking about different endocrine therapies, etc, in the metastatic setting, and a very interesting trial from MD Anderson, looking at not even doing surgery and very low risk
Cancers and following patients over time. We can talk about some of that later, too. But I think that that’s unlikely to reach primetime at the moment. So I think it’s probably early to be really thinking about that. As part of our, I think, overall thinking there are a bunch of trials looking at
Antibody drug conjugates as I mentioned early so we have a first line trial for triple negative disease with that opodo Mab directs to Canada first line trial for hormone receptor positive disease after endocrine therapy with Sasa tuza. Map COVID T can and then we have trials that are looking at these
Drugs in earlier high risk disease as well but I think in the metastatic setting is where we really are pushing to try and use the drugs earlier and before more resistance develops. There’s also a whole host of new drugs. There’s a new trope too
Similar to Datto Botha Mab and Sasa cheese map. There’s a new trope to ADC that will be studied from a Collaboration with Merck and a company in China. And so those trials are going to be going going in 2024. So we thinking like, wow, there
Are so many drugs, Laura Hubbard is doing some studies looking at a new her to ADC and her to lo disease after TD XD. And also we’re doing a study in her to positive disease after PTSD. So there’s lots going on with this area of antibody drug conjugates
Targeted therapy for Herrmann disease, their hormone receptor positive disease, and new hormone therapy. So a lot of exciting things along with of course, our our eye spy trial, which is again, a lot of novel agents in that area, too. And, yeah, there’s a lot of interest in that. MD Anderson study
Results. Why China? It’s because that’s where the drug was, and Merck wanted to acquire that drug because they wanted to be competing there. If I could pull up I have to say that slides from Henry cure, I would do that. Let’s see. Cure omission
Surgery. Let’s see. Maybe I can pull it up quickly. Okay, omission of breast surgery. So let me share this. Maybe we can do this as our last discussion. Hopefully I have the right one up here. Yeah. Okay. So this is a really actually Henry Kerr was
At UCSF briefly. And then he went back to MD Anderson in and Houston. And that is where he is. And then one of the questions that came up is, why did so many drugs do dx d as a payload because Daiichi got a good technology of making these
Antibody drug conjugates that seemed to really work a good linker a good number of toxins per antibody, so then they just use the same toxin. And yes, it would be much better to have different payloads. And the trouble has been using different payloads that don’t cause terrible toxicity, neuropathy, I
Toxicity etc. So this is all complicated. Alright, so let’s talk about this study, as was asked by one of the attendees. So this was a idea of our mission of breast surgery after neoadjuvant systemic therapy for invasive cancer, it’s three year update. And the group is called the exceptional responders Study
Group, which they called it. And what they did was, they said, Okay, and we’re doing this as part of ice by two as you give neoadjuvant chemo, and then you do MRI imaging or mammogram and you do a biopsy and decide whether or not the patient
Really has any cancer left there or not. And we’re using that to try and de escalate treatment and ISI. So if you have a biopsy, that’s negative, after getting half of the treatment, maybe you could stop and go to surgery, because if you have a
PCR you do well. So they’re they’re showing that if you did a biopsy, and it was negative, the correlation with having a true pathologic complete response was very high. So they did a study multicenter, and they included women who are 40 years or older. And that’s really because younger women
Tend to have multifocal more aggressive cancers, you could have had a single triple negative tumor, or hurt you positive it had could be up to five centimeters, you could have had up to four abnormal axillary nodes on ultrasound, a lot of cancer, and then any clinical chosen neoadjuvant systemic
Therapy that’s NST. And the tumor had to shrink to less than or equal to two centimeters on final breast imaging. They excluded patients who had a prior cancer progression, distant metastases, big tumors, all the same things not being pregnant. So the idea was to say that they could whether or not
They could get a treatment response rate that was good at 12 months and not have local recurrence. And so they did a feasibility study and that seemed to be okay, so now they’re showing the follow up of the ipsilateral breast being free of treatment, I don’t know what they were calling their IBT
Are here, but see if I can get it to go backwards Yeah, I think that they’re basically they’re just looking at the ipsilateral breast recurrence and how much you have there as their eye BTR. So basically, they look for patients who had residual disease, nope, or a no residual
Disease by biopsy. And then they did no breast surgery and followed them for ipsilateral. breast tumor recurrence free survival, meaning you didn’t have any recurrence in that breast. And then if you had residual disease, either invasive or unsightly, then you had standard surgery. So that
Was I mean, it’s really a very novel approach. They had 58 patients in 50 patients enrolled. And of the patients 31 patients had a PCR by biopsy and imaging and breast surgery was admitted, 90 patients had standard of care. So 38%. So now
We’ve got 31 patients that we’re moving forward on. And these patients, of those patients, the 12% of the patients who are enrolled in the trial altogether, at node positive disease, but most had no negative disease, more than 50% are hurt to positive 42%, triple negative, why do we include that
Group, because ER positive doesn’t get very high path car rates. That’s why. So here’s the ipsilateral, breast tumor free survival among patients who didn’t have breast surgery at three years 100% of patients so nobody’s had any recurrence in breast an immediate follow up of 38 months. So that’s a median of
About three years. Very interesting data for this group of patients. They also looked at circulating tumor cells and circulating tumor DNA. And then they looked at that to patients who were CTC positive at baseline. They then were to were positive six months, one to 12 months. So they follow that
Along to try and see whether or not that would tell them about recurrence. And cgda was looked forward to look for biomarkers of resistance. And they only saw a little bit. So it wasn’t really all that helpful, actually, because they didn’t see a lot thankfully, because these patients had fabulous
Responses. So, you know, they couldn’t really use the circulating blood markers, because it was so limited. And at fit with 50 patients of which, you know, the percent I showed you earlier had PCRs, the results were very good. But it’s important to keep in mind this represents 31 patients and hurts
You positive disease with a pathologic complete response, you get a year of trustees a map, and parties a map if you’re giving both. So they those patients won’t have been very far away from having their herd to targeted therapy. So we need longer follow up and obviously larger studies in order to put
This into clinical practice. Before I ask you guys about this, one of the questions that came up in the let’s see if I can get out of here, stop sharing, okay, is when we said ki 67 Did I mean the keys exam, the first biopsy or after the
Surgery? And the study did not say, so you could have a chi ki 67 At the initial biopsy, which is what we use for eligibility generally, or at the time of surgery. Either one. So what did you think about that no surgery study?
Saya Jacob, MD: I thought it’s bold to think about no surgery, especially for node positive disease. I mean, it’s a really novel idea. And I think an important question. But yeah, I’m interested to see with more follow up what happens, but that struck me that some patients with note positives, and these
Would not get surgery. Hope Rugo, MD: How about you, Laura? Yeah, I Laura Huppert, MD: agree. I think that piece of it makes me nervous. I do think it’s not I mean, definitely not ready for primetime, but will be interesting to follow out. Some
Of these patients, especially with very low risk disease. I think I get this question a lot clinically for patients that are on the much older side, that don’t want surgery and sometimes even give endocrine therapy before surgery and their tumor seems to shrink away. And they’re like, Well, do I need to
Go to surgery? And I think there are settings where potentially consider not in those cases. And that’s something that’s an application where I think we might consider using data like this to help guide things. But right now, I don’t think it’s ready for primetime for most patients.
Hope Rugo, MD: One somebody asked in the q&a, why no surgery? Laura Huppert, MD: Why no surgery? Yeah. Some people don’t want surgery. Some people don’t want surgery. Many people don’t want surgery. I think fortunately, breast surgeries are often recoverable. But I think especially as people get
Older, it’s not something that everyone wants. So Hope Rugo, MD: then a corollary Laura, why do we not do surgery on patients who have stage four disease? Good question. Laura Huppert, MD: Um, so once the the tumor has spread beyond the breast and axillary lymph nodes, and it’s in the whole
Body, we have data that actually doing surgery to remove the tumor in the breast of the lymph nodes doesn’t help improve survival, basically, because we know that the tumor is already elsewhere. And that’s the disease elsewhere is actually what ends up you know, causing death for patients because the
Cancer in the breast is not the problem. It’s the fact that it can spread to other organs and caused organ dysfunction. And so rather than doing surgery to remove it in the breast, which isn’t going to help people live longer, we usually instead use systemic therapy which targets the cancer that’s everywhere.
Parts regularly the more problematic, you know, areas like the liver, the lungs, the brain, etc. Yeah, Hope Rugo, MD: now we can do radiation to target certain problematic areas, there’s a lot of interest in sometimes using radiation if you have a single metastatic site and everything
Is responding beautifully, although we don’t know that that improves outcome we’d like to believe it does. And it’s very hard to you know, it’s individual patient versus a large population. And the studies that have been done have included like all different cancer subtypes, and, you know,
There may be subtypes that benefit more than others. And of course, the whole question, this person asked if there’s no surgery want to keep on spreading, no, not for metastatic disease, because there are cells that we don’t see. So if you remove the primary tumor, which the idea
Was that maybe that’s where all the cancer came from, actually, the cancer is sitting in lots of other places. So it just moves around, it doesn’t actually help and you have to stop therapy to do the surgery. And it’s often quite disfiguring. And so the
Whole idea of doing a bunch of surgery that isn’t going to help you to live longer is then that’s really where that came up. Now, I will say that somebody has hurt you positive metastatic disease who has, you know, basically all their cancer goes away for several years. If there’s a concern about
Something in the breast, that might be one situation where you might do breast surgery, but generally we don’t. And if you have a single liver lesion now we can target it with radiation therapy as appropriate, as after a response to systemic therapy
Because if you just target each one so called berry picking, or cherry picking vote, then it just pops up next to it it’s like Whack a Mole you know, it doesn’t work so but you know, we’re learning lots of new things and following and trying
To figure out how to further improve things and you know, use radiation to stimulate immune system and help immunotherapy many different areas. And we’ll tell you more about breast cancer and the updates in early January when we review the San Antonio Breast Cancer meeting. Hopefully both Lauren saya will
Be there saya is going to have her first child in sometime in January, January. And first babies are rarely early. So we’ll see. But excellent, excellent presentations. Both of you so appreciate your time after a long day in clinic and all of you the participants in for the somebody’s raising their
Hand but the participants of the forum for your questions for your participation for your support, and of course a melody for without whom we wouldn’t have the forum. So thank you so much, everybody. I look forward to talking to you in January. Happy end of your year, holidays, New Year, etc. and be
Safe and well. Take care