SABCS 2023 Breast Cancer Highlights – NSABP B-51, IDEA Update, ICARO, Keynote 522 Update

Welcome to SABCS 2023 Highlights and NSABP B-51 Hello everyone I am Rahul Gosain. Speaker 2 And I'm Rohit Gosain. Speaker 1 And we are oncology brothers, San Antonio Breast Cancer Symposium 2023 had a lot of data to cover practice informing and practice changing studies from this symposium, particularly the escalation of radiation and surgical interventions and then focus on Keynote 52 study in early triple negative breast cancer. Today we're joined by Doctor Eleanora toplenski from Valley Health in New Jersey. Eleanora, welcome. Speaker 3 Thank you. Thank you so much for having me. Lots to discuss here. Speaker 2 Eleanora, thanks for joining us. Eleanora, our first study out of the few studies that we will be discussing which will be more about DE escalation of radiation or axillary lymph node dissection after initial neoadjuvant treatment starting off with NS A/B PB51 study. Can you please walk us through the study design and its findings? Speaker 3 Absolutely. And I think it's important to know that you know that we've been doing a lot of escalation of care in recent years. So de escalation and trying to minimize toxicity is really important. So this study NSAV PB51 really looks to see is if someone is clinically node positive and then they become lymph node negative after neoadjuvant chemotherapy, is there a benefit to adding regional nodal radiation. So what they had in this study patients were clinically T1 to T3 and one. So again not a significant lymph node burden, no evidence of metastatic disease. They were receiving at least eight weeks weeks of neoadjuvant chemotherapy with anti her two therapy. They were her two positive and then they had surgery either lumpectomy or mastectomy And at the time of surgery if they were, if their lymph nodes were negative then they were randomized and then or regional nodal radiation, R and I with breast radiation again if they had a lumpectomy or chest wall radiation if they had a mastectomy. Speaker 2 So again, we continue to talk about this theme about doing more is not always a good thing. So what did the studies show so? Speaker 3 What we found was, as you can see here that there was actually no difference in either invasive breast cancer recurrence free interval or distant recurrence free interval whether you ended up having regional nodal radiation or not having regional nodal radiation. And I I think that these results are really significant because because you know they had a very long about almost five year mediation follow up. A lot of these patients were her two positive or triple negative where they do experience, you know recurrences in this time period. And it tells us that if you are having small lymph node burden clinically and one and become pathologically node negative that at least according to the study there's really no difference in adding regional nodal radiation. So I think that this is practice changing. You know the one thing that's important to keep in mind is that they had to have at least two lymph nodes removed at the time of the surgery. So just removing one lymph node would not, you know, be significant. Speaker 1 Eleonora, thank you for covering that. Just to reiterate few things that you've covered. This was not only endocrine positive patient population but also included her two positive patients and as if now the standard of care is to consider regional nodal radiation. So moving forward, this is indeed practice changing because you can technically emit regional radiation for a certain patient population. De-escalating Radiation with the IDEA Trial Update All right. Now moving forward to another study IDEA trial, we also have IDEA trial in colon cancer looking at duration of adjuvant chemotherapy. Of course our focus here today is breast cancer. In this trial we look at completely emitting radiation in select stage 1 hormone receptor positive post menopausal woman who've undergone a breast conserving surgery. Also these patients had low ONCO type score. Eleanora, your thoughts here I. Speaker 3 Think this study is really important. You know, we have data to support omitting radiation in patients younger than 70 and I think what we're realizing you know is that age is certainly one factor, but the biology matters as well. And So what they did in this study, they really pick a low risk population. You know the average here was 62, they had a mean tumor size of 10mm, they were node negative, their Oncotype was low at 11. And and you know what's important here is that only about a third of them had MRI. So I think that's a key point because you know I think could some of them have had more disease. What they found was that you know all of these patients really did remarkably well at five years overall and breast cancer specific survival was both 100 percent and five year freedom from any recurrence was 99%. So you know this is not a randomized study. They had this population again low risk population where they omitted radiation, I'm sorry, yeah, where they omitted radiation. And again this is kind of supporting that de escalation of care. Now randomized trial is ongoing that I think will better answer this question, but I think that it it's something that we should be considering and discussing with patients. They the key here is that in this population they actually had a fairly high compliance rate of endocrine therapy. And so this is probably something that we would not want to de escalate and someone who were worried about how they're going to tolerate endocrine therapy or they're not sure about whether they would want to take endocrine therapy or not. And it kind of again goes to say that we really have to optimize compliance to endocrine therapy by starting to better manage some of our side effects so that maybe we can omit you know, radiation in the future. Speaker 2 Thanks very much for covering that. And again just to reiterate, both of these studies have had good amount of follow up and both of them are arguing against doing more is not always good. So it is important to see how patients are responding, so appropriate treatment can be advised. ICARO Study: Omitting Axillary Dissection Post-NAC Now staying on the same topic similar to NSABP, now we have IKARO study also looks at what to do after neoadjuvant chemotherapy in no positive patient population. If you do have residual disease that is isolated tumor cells in Sentinel lymph node or a clip node. Eleanora, your take away from this study. Speaker 3 So this study kind of again similar to an SAVP 51, but here instead of looking at you know clinically apparent lymph nodes, we're seeing patients who on central lymph node biopsy had isolated tumor cells. It's a small number of patients that have this, but this was a big say. They were able to accrue a large number of patients here with isolated tumor cells on central lymph node biopsy and then they kind of split them up again to those who had axillary lymph node dissection and those who did not have axillary lymph node dissection. Now here the follow up is a little bit shorter than we saw in NSAP 51, it's only about three years. So we'll kind of sneed to see a little bit longer term follow up. But what they showed was that there was no difference in five year rate of invasive recurrence whether you had axillary lymph node dissection or did not have axillary lymph node dissection. You can see here it was 19% for no ALND versus 16% for axillary lymph node dissection and it was not statistically significant. So this I think also was practice changing and really does not support the addition of axillary lymph node dissection for patients with isolated tumor cells. Speaker 1 Eleanora, thank you. You brought up that this is not a common population and absolutely the problem ends up being that at tumor boards or when we see these patients, we're always struggling saying what next and we often end up over treating these patients. So again, this ends up supporting that maybe we can forgo that axillary lymph node dissection because that in itself has a lot of quality of life problems for our patients. Speaker 3 And I think this is really reassuring. All these studies are really reassuring for patients because there is almost this fear of de escalation. And I think having really robust data to support what we're doing really I think will provide additional reassurance for patients. Speaker 2 And I think we do get hesitant especially when we are dealing with younger population. We don't want to under treat them. And again, Raul, to your point about side effects, we tend to run into this issue more commonly because if you are in the tertiary care center, there are lymphedema clinics, while if you're practicing in rural or community settings, we are much restricted with that. Speaker 1 Absolutely. No, that that's exact coming back to our patient population that we're serving close to home. These are the struggles that we see day in, day out. KEYNOTE-522 Update: TNBC Immunotherapy Standard of Care All right. Now let's switch gears to focus on triple negative breast cancer. Since 2021, PERIOP immunotherapy with neoadjuvant chemotherapy and then adjuvant immunotherapy has been our standard of care. After KEYNOTE 5 to 2, Eleanora, before I even jump on the recent study updates, I feel like if you were to talk to five oncologist about this regimen, every single one has their own little tweaks on how to give this. Some are sequencing the chemotherapy a little different than some are giving AC every two weeks versus 3 weeks. How do you prescribe this regimen in your clinic? Speaker 3 Yeah. So this great, great question. I think when it came out, you know everyone kind of followed the protocol exactly and then you start again, you said you'd pick up these little things and you start to tweak it. So you know I do do carbopa and impactly taxol first with pembrolizumab. I find that if we've in certain cases we've done AC 1st and we've just kind of run into a lot more myelosuppression toward the end of the Carbotaxel kind of not allowing us to finish it. So still do the Carbotaxol with the KEYTRUDA and when we get to the ACI still for the most part I have done the every three weeks only because it's just a lot for patients to come if they use due to the dose dent AC and then the KEYTRUDA doesn't always line up and a lot of them prefer just to come once every three weeks and and be you know kind of it's a little bit easier. But there are certain cases where I found that you know the duration of neutropenia in without without growth factor in the every three weeks, you know it's prolonged And so people actually start to experience more malaise and more fatigue just with that prolonged neutropenia. So in certain cases I have either done the dose stance, you know and added the growth factor. But though that's kind of how I do it, I still typically do follow the protocol, but we do tweak it. And I've had certain cases where you know, if we have an older patient, we'll do the Carbotaxol with the Keytruda and then maybe evaluate for surgery if we're worried about giving the anthracycline, you know, in some cases we've omitted the carboplatin depending on toxicity and and myelous oppressions. So I think, you know, there's a protocol and then there is looking at your patient and saying, OK, what can you tolerate, what are your comorbidities, what's your age mean? All of these things to really make sure that we know this regimen is really effective and practice changing. But we also want to make sure our patient, you know, has as maintain as much of A quality of life and feel as you know, good as we can during the process. Speaker 2 And even in my practice we do use TC upfront followed by AC because we have to keep in mind that we are going with a curative intent and the quality of life has to paramount everything. OK, Coming back to the recent data, Eleanora, what did the updates really show? Speaker 3 So I think the updates were really quite significant. And what they show here is that there's a benefit to addition of pembrolizumab, so following Keno 5/22 for patients and they broke it down both by clinically by negative nodal status and by positive nodal status and then also by stage two versus stage 3. And they also did a longer event free survival update and it all shows that regardless of nodal status, regardless of the benefit to the addition of pembrolizumab. And when you look at the updated event free survival, you know it's it's almost 10% increase with the addition of pembrolizumab. So I think that this really further reinforces the addition of pembrolizumab and sometimes one of the things that we hear is people are hesitant to give this, you know, it's, it's an intensive regimen and immunotherapy is certainly not without its side effects and people are hesitant to give it in that T2N0 sometimes like oh do they really need it, You know, they have a 2.1cm, no negative cancer. This really actually supports that this population definitely should be getting it and kind of raises the question is, you know, is there a benefit to someone who's AT1C no negative, no, we don't have data to support that. But you know, I think this really kind of just reinforces and you know, provides more data to be using it in that stage two, stage 3 triple negative breast cancer. Speaker 1 If these results are definitely encouraging and this will continue to remain our standard of care, you know first half of the discussion here we're talking about de escalation and every single time we've brought up Keynote 5 to 2, I always bring this up. So Eleonora, how much is IO helping in adjuvant settings? If you have obtained PCR and you brought this up, immunotherapy has its own side effects, they're not rare. Speaker 3 Yeah. I think that's a question that we still don't know the answer to. There is an ongoing study looking at de escalation of IO in the adjuvant setting if someone has achieved APCR but you know with the updated data here they show that even if you have achieved APCR that there is a benefit, a significant benefit to pembrolizumab. So it's not you know we it's not just about achieving PCR, the drugs that you're taking to get there actually matter. So I think that we're not there yet in pulling back IO in the adjuvant setting. I'll be very interested to see what the ongoing research. Speaker 2 And thanks so much for covering that Eleanora, because we do run into this conversation where when talking to patients, they ask is this necessary and adjuvant setting. And now at least until we find out with this other study reporting these outcomes whether there is truly a benefit for now KEYNOTE 5 to 2 update definitely confirms that that there is additional benefit As a result we should continue and complete that one year of therapy. Speaker 3 Exactly. Speaker 2 We certainly do need better markers so that we can avoid or treatment in some of these patients. SABCS 2023 Key Studies Recap and Final Thoughts Well, Eleanora, thank you so much for joining us and covering these four critical studies from SABCS 2023 for our listeners. Stay tuned for a quick recap. Speaker 3 Thank you for having me. Speaker 2 We have covered 4 studies from SABCS 2023 with Doctor Eleanora Taplinsky from Valley Health. A big focus was on DE escalating radiation and node dissection in adjuvant settings based off of the first study NS A/B, PB51. There was no significant benefit in regional nodal irradiation if neoadjuvant chemotherapy resulted in node positive disease to node negative disease. Similarly, in the IKARO study, if there was only isolated tumor cells left behind after neoadjuvant chemotherapy, the additional axillary lymph node benefit was limited. Speaker 1 We also covered IDEA trial in breast cancer. We're omitting radiation in selected stage 1 hormone receptor positive. Post menopausal women with low Oncotype DX was deemed safe at last. We also focused on a recent update from Keynote 522, reiterating this as the current standard of care for early triple negative breast cancer with immunotherapy and chemotherapy. Speaker 2 Make sure to also check out our discussions with Doctor Hope Rugo and Doctor Daniel Strober covering other key studies from SABCS 2023. Thanks for joining. We are the oncology brothers.