How to Treat Triple Negative Breast Cancer - Discussion with Dr. Virginia Kaklamani

Early stage triple negative breast cancer Hello and welcome back to the Oncology Brothers Podcast. I'm Rahul Ghosain here with my brother and Co host Rohit Ghosain. In 2024, we've covered treatment algorithms for various disease sites and a lot has happened since then. Now in 2025, we're back again to dive into the advances and reiterate the current standard of care, focusing on what these new changes mean for us and our patients in the community settings. Starting off with triple negative breast cancer, today we have the pleasure of speaking with Doctor Virginia Catlamani from the UT Health San Antonio MD Anderson Cancer Center. Virginia, congratulations on another successful SABCS, especially as a chair. It's great to have you here today and I'm looking forward to our discussion around triple negative breast cancer. Speaker 2 Thank you. Thanks for having me. Speaker 3 Virginia, it's great to have you with us today. Let's get started. First off is the early stage triple negative breast cancer where the tumor sizes generally less than 2cm and no nodal involvement. What is your treatment paradigm like here? Speaker 2 So it's smaller tumors, less than 5mm. It's really a discussion with the patient. Most of these patients will go to RT. There was actually some data presented at SABCS suggesting that even these tumors have a higher risk of recurrence. So even though we've we've never had enough cases to find significant benefit of chemotherapy, when you look at the curves, they separate. But I do discuss chemotherapy with these patients, but the majority of them are not going to get chemotherapy. The 6mm to 1 centimeter I typically give chemotherapy and I will give a non anthracycline regimen with TC times 4. And then the T1C tumors. This is where there's a lot of debate. There's people that will give the keynote five to two regimen. There's people that are just going to give TC4. There's people that will give T carbo for four cycles and people that will give ACT. Some people will treat patients new adjuvantly and this is what I've I've started doing. I'll give them new adjuvant therapy, maybe give them the 1st 4 cycles of T carbo, see what the response looks like and then make decisions. But this is very controversial. Speaker 1 Virginia, even if you're getting through surgery and let's say 6mm to 1 centimeter, but the disease ends up being a little larger than what you expected in adjuvant settings, were the right patients that you're leaning towards anthracycline? Is it the bigger tumor? Of course, yes, if it's lymph node positive. But is it the bigger tumor grade younger patients? When are you bringing in anthracyclines here? Speaker 2 So for the triple negative breast cancers, most of them are going to be grade 3. So I don't really think of of of grade of the tumor as as the reason to give an anthracycline. The data with anthracycline and taxing really starts from T2 or node positive disease. We're extrapolating from that data, but we know based on a lot of prognostic data that these patients have a worse prognosis than we initially thought. So those are the patients the T1 CS that are likely bring in after cycling to. But there are ongoing trials looking at T carbo instead of the anthracycline, which obviously for the sake of leukemia and cardio toxicity is more preferable. Speaker 1 Absolutely. All right. Moving along to locally advanced triple negative breast cancer, where in recent years, especially with the inclusion of immunotherapy, we've seen the shift towards neoadjuvant treatment based off Keynote 5T2 regimen. Locally advanced triple-negative breast cancer And again just as a reminder, Keno 5T2 regimen is made of carboplatin, pathotaxel, adriamycin, cytoxan while we continue with pembrolizumab in the neoadjuvant and then we complete a year long of pembrolizumab post surgery. At SABCS 2024, we also saw that we don't have a clear biomarker in selecting the right patient for chemo immunotherapy, but this approach has led to pathological complete response and overall survival. So still remains your standard of care Virginia when it comes to disease that is 2cm or lymph node positive disease, your treatment here. Speaker 2 I think this is the one place where we actually have a standard therapy. We we don't really have a lot of argument as to what to do. So I'll give Keynote five to two complete surgery after surgery if there is APCR unlikely continue the pembrolizumab unless there's a lot of immune toxicity where I won't because we don't have data that pembro will help in those patients with PCR post surgery. If we if we don't have APCR, then I will combine pembrolizumab with either tapesitamine or a lab rib depending on whether the tumor is germline BRCA positive or not. I will probably also give a lab rib to those few patients that have a PAL B2 mutation. We don't have data, but this is another gene in that HRD pathway where we know PARP inhibitors are beneficial. We've seen the data in the metastatic setting. So I will extrapolate from that data and give a lab rib in that population. Speaker 3 Thanks for laying that Virginia and truly the consensus is utilizing Keynote 522 regimen. Now if the patient is not a candidate for IO, and I can certainly think of some of these patients in my clinic setting that is severe autoimmune disorder or a transplant patient in those settings for new adjuvant chemotherapy, do you still rely on dose dense ACT or carboplatin plus AC? Adjuvant chemotherapy for stage 2+ breast cancer Taxol is your preferred approach. Speaker 2 I definitely had carboplatin. I think we've seen now a lot of data from several clinical trials including meta analysis suggesting that triple negative breast cancer patients with a stage 2 plus tumor do get benefit from carbo. So I will add carbo. Now there's a debate whether to do AC followed by T carbo or T carbo followed by AC. I'll probably follow the keynote five to two regimen minus the pembro. Speaker 1 And Roy, you brought up those dense AC when not using immunotherapy as we have data supporting that those dense AC has better outcomes. But with keno 5T2 study, AC is given every three weeks. Virginia, in your practice, do you use those dense AC when relying on keno 5T2 regimen with femoralizumab? Speaker 2 I don't because the schedule ends up becoming a nightmare. You have them were given every three weeks and the AC given every two weeks and the study was really done with every three-week AC. So I'll give that. Speaker 1 Virginia, can I clarify something? You brought up a lab prep. We have updated data from Mesa BCS 2024 on Olympia. We continue to see overall survival benefit here. Do you combine the lab prep with pembrolizumab? I feel very comfortable with that approach with Cape sitabine and pembrolizumab. But patients with backup positive, do you just rely on PARP inhibitor and then come back to immunotherapy? Do you combine both of them? Speaker 2 I combine them. We have good safety data. There's a suggestion of synergy between the two. So I feel very comfortable combining those two. Speaker 3 OK. And while we are on that topic, with regards to if the patient is a bracha mutation positive residual disease, your approach? Speaker 2 Is I would not give Cape Sidabine in those patients, I would give the elaborabine Pembroke. Speaker 3 Thanks so much for covering that, Virginia. While we're talking about the Laparib and Cape Sidabine here, toxicity is diarrhea with regards to pembrolizumab can cause diarrhea, Cape Sidabine can cause diarrhea. Toxicity of Pembrolizumab and Capecizumab How do you navigate through that when you are treating with a combination itself? Do you taper one or the other or how do you go about that? Speaker 2 So the pembrolism of induced diarrhea is very different because it's immuno immunologic in nature, you have to add steroids and so forth. What we've seen with Keynote is that the majority of these immune related toxicities happen in the neoadjuvant setting. If a patient gets to the adjuvant setting without any neoadjuvant IO toxicity, it's unlikely that they will get this. But any doubt I will do a colonoscopy and biopsies because I need to know what the mechanism between behind the two is before I'm able to treat the patient. This is not IO related. I don't want to be giving steroids to these patients because then I'm increasing the likelihood of perforations, other other toxicities as well. Now the one thing that I haven't done yet in the adjuvant setting, unless somebody has toxicity is use the fixed dose of Cape cider being week on week off. I typically try to do the create X 2000 milligrams, not 2500 per meter square, but three weeks on, one week off. Once I see toxicity, I will switch. So that's fixed dose. Speaker 1 And while we're talking about Cape Cytobine and how to manage toxicities, another thing when it comes to supportive care is the Voltaren gel that can help with hand foot syndrome, something that I'm starting to use more and more in my practice. OK, before we switch gears to metastatic disease, low ERPR disease where expression is less than 10%, we often treat these patients as triple negative breast cancer. Low ERPR disease So a patient who received Keynote 5T2 regimen Virginia, do you still consider giving adjuvant endocrine therapy or completing a year of pembrolizumab is good enough? Speaker 2 So anybody that has ER more than 0% I will attempt to give endocrine therapy to. As an example. I just saw a patient in clinic today. She was ER 0, PR 8% and had finished the keynote regimen, had APCR, came to see me switch providers and I said I'd like to give you endocrine therapy with an AI. She argued with me. I said let's try it. If you have a lot of toxicities, perfectly happy to stop it. I think most of the benefits rose from chemotherapy. There's some ER positivity there. I'd like to give some endocrine therapy. There's the setting of a lot of these patients potentially needing AC DK46 inhibitor. So that's where the issue comes because they're low ER, right? They might need a CDK. What do we do? Do we give immunotherapy and CDK? The answer is no, especially with abemaciclib. There's actually some data suggesting increased toxicity with ILD. So we don't want to give the Enbrel and abemaciclib. We're going to have to make a decision as to which one to give. Maybe we give the pembro for the year and then we give the abemaciclib. Speaker 3 With the data on Ribo, would you still hold off on Ribo or any CDK 4/6 for that matter? Speaker 2 It it is because all of them are associated with IoD at a different extent, but they're all associated with a potential IoD. Speaker 1 Thanks for bringing that up because that was not on my radar, but very important now that these CDK 46 inhibitors are approved in adjuvant settings. All right, metastatic disease where immunotherapy is part of our treatment, but based off CPS score, whereas in locally advanced when we're covering Keno 522, the approval is regardless of PDO 1 score. Immunotherapy in metastatic disease Virginia, your approach here in de Novo metastatic disease. Speaker 2 So this is exactly what I will do. I will check for PDL one. If PDL 1 positive, I'll give pembrolizumab and chemotherapy. PDL one negative, I will give either chemotherapy or if a patient is germline bracha positive, I'll give a PARP inhibitor. Here we also have telesoparib approved, so I'll give one of the two. The question is, if they're PDL 1 positive and germ line Bracha positive, what do we give first? I'll give the pembro first because that's where we have the data and first line immunotherapy. In my second line, I will give the PARP inhibitor. Afterwards, we will likely start giving an antibody drug conjugate succitism up for triple negative is my favorite because the data is really more concrete. They're not as many patients with CDXD on Destiny breast or four really around 60 patients, 58 to be exact. So I wouldn't necessarily give that, but I would definitely consider it as my second line therapy. Speaker 3 Exciting to see the 2nd and 3rd and even fourth line options available with the sequencing what we have here, Virginia going back to our frontline option, we're based on Keynote 522 regimen which is being utilized in our locally advanced patient. Now this patient was to have a recurring disease or progressive disease. Recommendations for immunotherapy in advanced disease If the patient has completed immunotherapy now, is there a time frame that you wait for them to reconsider immunotherapy, that is 6 months or less than six months? Would you consider? Speaker 2 I would consider immunotherapy again because for the triple negative breast cancer metastatic, we don't have a lot of amazing oxygen options. So we really try to milk every option we have. These patients, assuming that they don't have any IO toxicities in the new adjuvant and adjuvant settings, they have metastatic disease and Spiegel 1 positive. I usually give pembrolizumab. I'll try to switch the chemotherapy around and that's one of the bigger issues that we have. They've received AC, they've received carboplatin and a taxane. So what do we give carbo GEM? Probably I don't want to give single agent taxane, but they've already seen carbo. So that becomes a little bit more of an issue. But this is the data that we have honestly. Speaker 1 And Rohit, this is a very aggressive disease that we're talking about. And Virginia, you touched on second and third line sequencing with Sasitismab. Sasitismab vs. TDXD TDXD. The big thing for us in the community ends up being managing toxicities when it comes to these two agents, be it neutropenia with Sasitismab, looking out for nausea, fatigue and ILD for TDXD. Any any clinical pearls around these two agents? Speaker 2 Yeah, absolutely. So Sasitismab I will give a growth factor on day 8 either on pro or day day 9 long acting GCSF and that really prevents me from having to delay cycle to day one. As far as diarrhea really hasn't becoming a major issue, we we will. My nurses I know will give atropine to some of these patients. They've been using it with irinotecan with good success. But that's for a cute diarrhea that doesn't really happen very often. We get the more chronic diarrhea, but it hasn't seemed to be an issues for me to prophylax patients. I always think Constipation is worse than area, so I'd rather get a little bit of diarrhea before I act on it. As far as TDXDA, couple of things. First of all, the major toxicity is going to be nausea, and we treat it as a highly metagenic regimen. We're going to give olanzapine. We're going to give all of our big guns, at least to start with. We can always dial back with cycle 2 if patients are doing well. The monitoring for ILD becomes a little tricky because we're supposed to do monitoring every six weeks, so that's two cycles and then every four cycles we are supposed to get scans for everything. So that's a lot of scans. On top of the fact that ILD doesn't appear within the first couple cycles. The median time to ILD is 8 to 10 months. So we're going to have to do a lot of CT scan. So what do we do? We have data now from several studies with risk factors for ILD and those are previous ILD. Any lung comorbidities, O2 SAT's of less than 95%, kidney insufficiency, potentially liver insufficiency, that's kind of most of what that data shows. So if I have patients with those risk factors, I will do my scans every six weeks and I actually documented because there's no way I'm going to remember. But if I don't have patients with those risk factors, I will say low risk for ILD and I'll do scans every nine weeks. Speaker 3 Thanks so much for pointing that out. In our practice, we do it as 2 1/2 months to three months, depending on the insurance approval as well. But yes, the trial did say to do it every six weeks. The cough or shortness of breath should not be taken lightly because there is mortality associated with it. And to what you pointed out, Virginia sassitusumab reusing growth factors because of the concerns of neutropenic fever. Getting comfortable and appreciating these nuances in how to manage some of these toxicities, an extremely important thing. Virginia, thank you so much for laying this foundation for triple negative breast cancer and talking through these clinical portals for our listeners. Let us go or a quick recap. Recap As we kick off 2025, the oncology landscape continues to evolve rapidly. We saw close to 50 new indications or drug approvals in 2024. What does this mean for us in our clinical practice? Where does this all fit in? We're back with our treatment algorithms to touch on the current standard of care and talk about these recent advances, starting off with triple negative breast cancer with doctor Virginia Kakamani. Speaker 3 Rahul, this is also shortly right after SABCS 2024. So I'm glad we were able to touch on some of the highlights from that conference. My key takeaways from today's discussion are certainly Keynote 522 where we are using chemotherapy and immunotherapy for locally advanced disease. This remains the current standard of care for a patient with 2cm or lymph node positive disease, though Doctor Keklamani did mention some consideration in one to 2cm as well. Speaker 1 Rohit, the important thing here is this is regardless of PDL one or CPS score because the approval for immunotherapy in metastatic disease is indeed for patients with CPS score of 10 and above. Speaker 3 Certainly and then role of sassatusumab and TDXD in metastatic space. While we have to be mindful about the toxicity around these agents. We hope you enjoyed this episode. Stay tuned for more discussions around the treatment algorithms, FDA approvals and toxic with us. We are the oncology brothers.