Podcasts about tnbc

We review the recent ASCENT-04/Keynote-D19 publication of sacituzuab govitecan + pembrolizumab for PD-L1 CPS of 10% and above TNBC compared to chemo + pembrolizumab alone. Also, a quick recap of ASCO GI earlier this month with mentions of zanidatamab and zolbetuximab. Finally, a check-in on The Pitt.

Featuring perspectives from Dr Javier Cortés, Dr Rita Nanda, Prof Peter Schmid and Dr Priyanka Sharma, including the following topics:  Introduction (0:00) Case: A woman in her early 80s with multiple comorbidities and triple-negative breast cancer (TNBC) develops bone-only metastases 4 months after declining capecitabine for post-neoadjuvant residual disease — Justin Favaro, MD, PhD (1:50) Case: A woman in her mid 70s with ER-negative, HER2-low (IHC 1+), PIK3CA-mutated, PD-L1-positive metastatic breast cancer (mBC) after receiving 3 cycles of neoadjuvant paclitaxel/carboplatin/pembrolizumab, which was discontinued — Alan Astrow, MD (6:47) Previously Untreated Metastatic TNBC (mTNBC) — Prof Schmid (10:47)  Case: A woman in her early 80s with multiregimen-recurrent ER-positive, HER2-low (IHC 1+) ESR1-mutant mBC receives sacituzumab govitecan — Jennifer Yannucci, MD (27:19) Case: The role of datopotamab deruxtecan (Dato-DXd) for patients with ER-positive, HER2-low mBC who experienced disease progression on prior trastuzumab deruxtecan (T-DXd) — Ranju Gupta, MD; Case: A woman in her late 70s with bilateral recurrence in the lungs of ER-negative, HER2-low (IHC 1+) breast cancer (PD-L1 TPS 20%) receives Dato-DXd with durvalumab on protocol — Yanjun Ma, MD, PhD (31:35) Integrating Antibody-Drug Conjugates (ADCs) into the Management of Endocrine-Resistant Hormone Receptor-Positive mBC — Dr Sharma (36:31) Case: A woman in her early 70s with recurrent ER-negative, HER2-low (IHC 2+) mBC receives sacituzumab govitecan and achieves complete remission — Dr Gupta; Case: Management of neutropenia associated with sacituzumab govitecan — Gigi Chen, MD (50:30) Case: A woman in her late 60s with recurrent ER-negative, HER2-low (IHC 1+) mBC (HER2 V69L mutation) receives T-DXd and achieves a complete response but develops Grade 1 interstitial lung disease — Dr Gupta; Case: Management of T-DXd-related side effects — Laila Agrawal, MD (54:10) Selection and Sequencing of Therapy for Relapsed/Refractory mTNBC — Dr Nanda (58:59) Case: A woman in her early 40s with multiregimen-recurrent ER-positive, HER2-low mBC who has experienced severe nausea with past treatments is about to initiate T-DXd — Atif M Hussein, MD, MMM (1:12:40) Tolerability and Other Practical Considerations with ADCs and Other Cytotoxic Agents for mBC — Dr Cortés (1:18:10) CME information and select publications

Dr. Monty Pal and Dr. Hope Rugo discuss advances in antibody-drug conjugates for various breast cancer types as well as treatment strategies in the new era of oral SERDs for HR-positive breast cancer. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and vice chair of academic affairs here at the City of Hope Comprehensive Cancer Center, Los Angeles. Today, I'm thrilled to be joined by Dr. Hope Rugo, an internationally renowned breast medical oncologist and my colleague here at City of Hope, where she leads the Women's Cancers Program and serves as division chief of breast medical oncology. Dr. Rugo is going to share with us exciting advances in antibody-drug conjugates (ADCs) that are expanding treatment options in various breast cancer types. She'll also address some of the complex questions arising in the new era of oral SERDs (selective estrogen receptor degraders) that are revolutionizing treatment in the hormone receptor-positive breast cancer space. Our full disclosures are available in the transcript of this episode.  Dr. Rugo, welcome, and thanks so much for being on the podcast today. Dr. Hope Rugo: Thank you. Pleasure to be here. Dr. Monty Pal: So, I'm going to switch to first names if you don't mind.  The first topic is actually a really exciting one, Hope, and this is antibody-drug conjugates. I don't know if I've ever shared this with you, but I actually started my training at UCLA, I was a med student and resident there, and it was in Dennis Slamon's lab. I worked very closely with Mark Pegram and a handful of others. This is right around the time I think a lot of HER2-directed therapies were really evolving initially in the clinics. Now we've got antibody-drug conjugates. Our audience is well-familiar with the mechanism there but tell us about how ADCs have really started to reshape therapy for HER2-positive breast cancer. Dr. Hope Rugo: Yeah, I mean, this is a really great place to start. I mean, we have had such major advances in breast cancer just this year, I think really changing the paradigm of treating patients. But HER2-positive disease, we've been used to having sequenced success of new agents. And I think the two biggest areas where we've made advances in HER2-positive disease, which were remarkably advanced this year in 2025, have been in antibody-drug conjugates with trastuzumab deruxtecan and with new oral tyrosine kinase inhibitors (TKIs) that have less of a target on EGFR and more on HER2, so they have an overall more tolerable toxicity profile and therefore a potentially better efficacy in the clinic. At least that's what we're seeing with these new strategies that we couldn't really pursue in the past because of toxicities of the oral TKIs. So, although our topic is ADCs, I'm going to include the TKI because it's so important in our thinking about treating HER2-positive disease. In the metastatic setting, we've seen these remarkable improvements in progression-free and overall survival in the second-line setting with T-DXd, or trastuzumab deruxtecan, compared to T-DM1. And then sequencing ADCs with giving T-DXd after T-DM1 was better than an oral tyrosine kinase or a trastuzumab combination with standard chemotherapy. That was DESTINY-Breast03 and DESTINY-Breast02. So, then we've had other trials since then, and T-DXd has moved into the early-stage setting, which I'll talk about in just a moment. But the next big trial for T-DXd in HER2-positive disease was moving it to the first-line setting to supplant what has become an established treatment for now quite a long time: the so-called CLEOPATRA regimen, which used the combined antibodies trastuzumab, pertuzumab with a taxane as first-line therapy. And then we've proceeded on with maintenance with ongoing HP for patients with responding or stable disease. And we'd seen long-term data showing, you know, at 8 years there was a group of patients whose cancers had never progressed and continued improved overall survival. So, T-DXd was studied in DESTINY-Breast09, either alone or in combination with pertuzumab compared to THP. The patient population had received a little bit more prior treatment, but interestingly, not a lot compared to CLEOPATRA. And they designed the trial to be T-DXd continued until progression with or without pertuzumab versus THP, which would go for six cycles and then stop around six cycles, and then stop and continue HP. Patients who had hormone receptor-positive disease could use hormone therapy, and this is one of the issues with this dataset because, surprisingly in this dataset and one other I'll mention, very few patients took hormone therapy. And even in the maintenance trial, the HER2CLIMB-05, less than 50% took hormone therapy as maintenance. This is kind of shocking to me and highlights an area of really important education, that outcome is improved when you add endocrine therapy for hormone receptor-positive HER2-positive metastatic disease in the maintenance phase, and it's a really important part of treatment. But suffice it to say, you know, you're kind of studying continued chemo versus stopping chemo in maintenance. And T-DXd, as we all expected, in combination with pertuzumab was superior to THP in terms of progression-free survival, really remarkably improved. And you could stop the chemo with toxicity, but most people continued it with T-DXd. Again, not a lot of people got hormone therapy, which is an issue, and you stop the chemo in the control arm. So, this has brought up a lot of interest in trying to use T-DXd as an induction and then go to maintenance, much as we do with the CLEOPATRA regimen with hormone therapy. But it brings up another issue. So first, T-DXd is superior; it's a great treatment. Not everybody needs to have it because we don't know whether it's better to give T-DXd first or second with progression - that we need a little bit longer follow-up. But just earlier this week, interestingly, the third week of December, the U.S. FDA approved T-DXd in the DESTINY-Breast09 approach with pertuzumab. So as I mentioned earlier, there was a T-DXd-alone arm; that arm has not yet reported. So very interesting, we don't know if you need pertuzumab or not. So what about the maintenance? That's the other area where we've made a huge advance here. So, we all want to stop chemo and we want to stop T-DXd. You don't want somebody being nauseated for two years while they're on treatment, and also there's a small number of patients with mostly de novo metastatic HER2-positive disease who are cured of their disease. We'd like to expand that, and I think these new drugs give us the opportunity to improve the number of patients who might be cured from metastatic disease. So the first maintenance study we saw was adding palbociclib, the CDK4/6 inhibitor, to endocrine therapy and HP, essentially. There, we had a remarkable improvement in progression-free survival difference of 15.2 months: 29 to 44 months, really huge. At San Antonio this year, we saw data with this oral tyrosine kinase inhibitor tucatinib, already showed it was great in a triplet, but as maintenance in combination with HP, it showed also a remarkable improvement in progression-free survival. But the numbers were all shifted down. So in PATINA, the control arm was in the 24-month range; here it was the tucatinib-HP arm that was in the 25 months and 16 months for control. So there was a differential benefit in ER-negative and ER-positive disease. So I think we're all thinking that our ideal approach moving forward would be to give T-DXd to most patients, we see how they do, and treat to best response. And then, stop the T-DXd, start HP, trastuzumab, pertuzumab for ER-negative, with tucatinib for ER-positive with palbociclib. We also have early data that suggests that both approaches may reduce the development of brain metastases, an issue in HER2-positive disease, and delay time to progression of brain metastases as seen in HER2CLIMB-05 in very early data - small numbers, but still quite intriguing that you might delay progression of brain metastases with tucatinib that clearly has efficacy in the brain.  So, I think that this is a hugely exciting advance for our patients, and these approaches are quickly moving into the early stage setting. T-DXd compared to standard chemo, essentially followed by THP, so a sequenced approach resulted in more pathologic complete responses than a standard THP-AC-type neoadjuvant therapy. T-DXd alone for eight cycles wasn't better, and that's interesting. We still need the sequenced non-cross-resistant chemo. But I think even more importantly, the data from DESTINY-Breast05 looking at T-DXd versus T-DM1 in patients with residual disease after neoadjuvant HER2-targeted therapy showed a remarkable improvement in invasive disease-free survival with T-DXd versus T-DM1, and quite early. It was a high-risk population, higher risk than the T-DM1 trial with KATHERINE, but earlier readout with a remarkable improvement in outcome. We expect to be FDA approved sometime in the first half of 2026. So then we'll get patients who've already had T-DXd who get metastatic disease. But my hope is that with T-DXd, maybe with tucatinib in the right group of patients or even sequenced in very high-risk disease, that we could cure many more patients with early-stage HER2-positive breast cancer and cure a subset, a greater subset of patients with de novo metastatic disease. Dr. Monty Pal: That's brilliant. And you tackled so many questions that I was going to follow up with there: brain metastases, etc. That was sort of looming in my mind. I mean, general thoughts on an ADC versus a TKI in the context of brain mets? Dr. Hope Rugo: Yeah, it's an interesting question because T-DXd has shown quite good efficacy in this setting. And tucatinib, of course, had a trial where they took patients with new brain mets, so a larger population than we've seen yet for the T-DXd trials, and saw that not only did they delay progression of brain metastases and result in shrinkage of existing untreated brain mets, but that patients who develop a new brain met, they could stay on the same assigned treatment. They got stereotactic radiation, and then the patients who were on tucatinib with trastuzumab and capecitabine had a further delay in progression of brain mets compared to those on the placebo arm, even after treatment of a new one that developed on treatment. So, I think it's hard. I think most of us for a lot of brain mets might start with the tucatinib approach, but T-DXd is also a very important treatment. You know, you're kind of trading off a diarrhea, some liver enzyme elevations with tucatinib versus nausea, which you really have to work on managing because it can be long-delayed nausea, and this risk of ILD, interstitial lung disease, that's about 12%, with most but not all trials showing a mortality rate from interstitial lung disease of just under 1 percent. In the early-stage setting, it was really interesting to see that with T-DXd getting four cycles in the neoadjuvant setting, a lot less ILD noted than the patients who got up to 14 cycles, as I think they got a median of 10 cycles in the post-surgical setting, there was a little bit more ILD. But I think we're going to be better and better at finding this earlier and preventing mortality by just stopping drug and treating earlier with steroids. Dr. Monty Pal: And this ILD issue, it always seems to resurface. There are drugs that I use in my kidney cancer clinic, everolimus, common to perhaps the breast cancer clinic as well, pembrolizumab, where I think the pattern of pneumonitis is quite different, right? What is your strategy for recognizing pneumonitis early in this context? Dr. Hope Rugo: Well, it is, and you know, having done the very early studies in everolimus where we gave it in the neoadjuvant setting and we're like, "Hmm, the patient came in with a cough. What's going on?" You know, we didn't know. And you have mouth sores, you know, we were learning about the drug as we were giving it. What we don't do with everolimus and CDK4/6 inhibitors, for example, is grade 1 changes like radiation pneumonitis, we don't stop, we don't treat it. We only treat for symptoms. But because of the mortality associated with T-DXd, albeit small, we stop drug for grade 1 imaging-only asymptomatic pneumonitis, and some of us treat with a half dose of steroids just to try and hasten recovery. We've actually now published or presented a couple of datasets from trials, a pooled analysis and a real-world analysis, that have looked at patients who were retreated after grade 1 pneumonitis or ILD and tolerated drug very well and none of them died of interstitial lung disease, which was really great to see because you can retreat safely and some of these patients stayed on for almost a year benefiting from treatment. So, there's a differential toxicity profile with these drugs and there are risk factors which clearly have identified those at higher risk: prior ILD, for example. A French group said smoking; other people haven't found that, maybe because they smoked more in France, I don't know. And being of Japanese descent is quite interesting. The studies just captured that you were treated in Japan, but I think it's probably being of Japanese descent with many drugs that increases your risk of ILD. And, you know, older patients, people who have hypoxia, those are the patients. So, how do we do this? With everolimus, we don't have specific monitoring. But for T-DXd we do; we do every nine weeks to start with and then every 12 weeks CT scans because most of the events occur relatively early. Somebody who's older and at higher risk now get the first CT at six weeks. Dr. Monty Pal: This is super helpful. And I have to tell you, a lot of these drugs are permeating the bladder cancer space which, you know, is ultimately going to be a component of my practice, so thank you for all this. We could probably stay on this topic of HER2-positive disease forever. I'm super interested in that space still. But let me shift gears a little bit and talk about triple-negative breast cancer and this evolving space of HR-positive, HER2-low breast cancer. I mean, tell us about ADCs in that very sort of other broad area. Dr. Hope Rugo: So triple-negative disease is the absolute hardest subset of disease that we have to treat because if you don't have a great response in the early stage setting, the median survival is very short, you know, under two years for the majority of TNBCs, with the exception of the small percentage of low proliferative disease subsets. The co-question is what do we do for these patients and how do we improve outcome? And sacituzumab govitecan has been one strategy in the later line setting that was shown to improve progression-free and overall survival, the Trop-2 ADC. We had recently three trials presented with the two ADCs, sacituzumab govitecan and the other Trop-2 ADC that's approved for HR-positive disease, datopotamab deruxtecan. And they were studied in the first-line setting. Two trials with SG, sacituzumab govitecan, those trials, one was PD-L1 positive, ASCENT-04. That showed that SG with a checkpoint inhibitor was superior, so pembrolizumab was superior to the standard KEYNOTE-355 type of treatment with either a taxane or gemcitabine and carboplatin with pembrolizumab for patients who have a combined positive score for PD-L1, 10 or greater. So, these are patients who are eligible for a checkpoint inhibitor, and SG resulted in an improved progression-free survival.  The interesting thing about that dataset is that few patients had received adjuvant or neoadjuvant checkpoint inhibitor, which is fascinating because we give it to everybody now. But access is an issue and timing of the study enrollment was an issue. The other thing which I think we've all really applauded Gilead for is that there was automatic crossover. So, you could get from the company, to try and overcome some of the enormous disparities worldwide in access to these life-saving drugs, you could get SG through the company for free once you had blinded independent central review confirmation of disease progression. Now, a lot of the people who got the SG got it through their insurance, they didn't bill the company, but 80 percent of patients in the control arm received SG in the second-line setting. So that impacts your ability to look at overall survival, but it's an incredibly important component of these trials. So then at ESMO, we saw the data from SG and Dato-DXd in the first-line metastatic setting for patients who either had PD-L1-negative disease or weren't eligible for an immunotherapy. For the Dato study, TROPION-Breast02, that was 10 percent of the patients who had PD-L1-positive disease but didn't get a checkpoint inhibitor, and for the ASCENT-03 trial population it was only 1 percent. Importantly, the trials allowed patients who relapsed within a year of receiving their treatment with curative intent, and the Dato study, TB-02, allowed patients who relapsed while on treatment or within the first six months, and that was 15 percent of the 20 percent of early relapsers. The ASCENT trial, ASCENT-03, had 20 percent who relapsed between 6 and 12 months. The drugs were better than standard of care chemotherapy, the ADCs in both trials, which is very nice. Different toxicity profiles, different dosing intervals, but better than standard of care chemotherapy in the disease that's hardest for us to treat. And importantly, when you looked at the subset of early relapsers, those patients also did better with the ADC versus chemotherapy, which is incredibly important. And we were really interested in that 15 percent of patients who had early relapse. I actually think that six months thing was totally contrived, invented, you know, categorization and doesn't make any sense, and we should drop it. But the early relapsers were 15 percent of TB-02 and Dato was superior to standard of care chemo. We like survival, but the ASCENT trial again allowed the crossover to an approved ADC that improved survival and 80 percent of patients crossed over. In the Dato trial, they did not allow crossover, they didn't provide Dato, which isn't approved for TNBC but is for HR-positive disease, and they didn't allow, of course, pay for SG. So very few patients actually crossed over in their post-treatment data and in that study, they were able to show a survival benefit. So actually, I think in the U.S. where we can use approved drugs already before there's a fixed FDA approval, that people are already switching to use SG or Dato in the first-line setting for metastatic TNBC that's both PD-L1 positive for SG and PD-L1 negative for both drugs. And I think understanding the toxicity profiles of the two drugs is really important as well as the dosing interval to try and figure out which drug to use. Dr. Monty Pal: Brilliant. Brilliant. Well, I'm going to shift gears a little bit. ADCs are a topic, again, just like HER2-positive disease we could stay on forever. Dr. Hope Rugo: Huge. Yes. Dr. Monty Pal: But we're going to shift gears to another massive topic, which is oral SERDs. In broad strokes, right, this utilization of CDK4/6 inhibitors in the context of HR-positive breast cancer is obviously, you know, a paradigm that's been well established at this point. Where do we sequence in oral SERDs? Where do they fit into this paradigm? Dr. Hope Rugo: Ha! This is a rapidly changing area; we keep changing what we're saying every other minute. And I think that there are three areas of great interest. So one is patients who develop ESR1 mutations that allow constitutive signaling through the estrogen receptor, even when there's not estrogen around, and that is a really important mutation that is subclonal; it develops under the pressure of treatment in about 40 percent of patients. And it doesn't happen when you first walk in the door. And what we've seen is that oral SERDs as single agents are better than standard single-agent endocrine therapy in that setting. The problem that we've had with that approach is that we're now really interested in giving targeted agents with our endocrine therapies, not just in the first-line setting where CDK4/6 inhibitors are our standard of care with survival benefit for ribociclib and, you know, survival benefit in subsets with other CDK4/6 inhibitors, and abemaciclib with a numeric improvement. So we give it first line. The question is, what do you do in the second-line setting? Because of the recent data, we now believe that oral SERDs should be really given with a targeted agent. And some datasets which were recently presented, which I think have helped us with that, have been EMBER-3 and then the most recently evERA BC, or evERA Breast Cancer, that looked at the oral SERD giredestrant with everolimus compared to standard of care endocrine therapy with everolimus, where 100 percent of patients received prior CDK4/6 inhibitor and showed a marked improvement in progression-free survival, including in the subsets of patients with a short response, 6-12 months of prior response to CDK4/6 inhibitor and in those who had a PIK3CA pathway mutation. The thing is that the benefit looks like it's much bigger in the ESR1 mutant population, although response was better, PFS wasn't better in the wild type. So, we're still trying to figure that out. We also saw EMBER-3 with imlunestrant and abemaciclib as a second line. Not everybody had had a prior CDK4/6 inhibitor; they compared it to imlunestrant alone, but still the data was quite striking and seemed to cross the need for ESR1 mutations. And then lastly, we saw data from the single arms of the ELEVATE trial looking at elacestrant with everolimus and abemaciclib and showed these really marked progression-free survival data, even though single-arm, that crossed the mutation status. At least for the everolimus combination, abemaciclib analysis is still to come in the mutated subgroups. But really remarkable PFS, much longer.  Single-agent fulvestrant after CDK4/6 inhibitor AI has a PFS in like the three-month range and in some studies, maybe close to five months. These are all at 10-plus months and really looking very good. And so those questions are, is it ESR1 mutation alone? Is it all comers? We'd like all comers, right? We believe in the combination approach and we're learning more about combinations with drugs like capivasertib and other drugs as we move forward. Everybody now wants to combine their targeted agent with an oral SERD because they're clearly here to stay with quite remarkable data. The other issue, so the second issue in the metastatic setting is, does it make a difference if we change to an oral SERD before radiographic imaging evidence of progression? And that was the question asked in the SERENA-6 trial where patients had serial monitoring for the presence of ESR1 mutations in ctDNA. And those who had them without progression on imaging could be randomized to switch to camizestrant with the same CDK4/6 inhibitor or stay on their same AI CDK4/6 inhibitor. And they showed a difference in progression-free survival that markedly favored camizestrant. But interestingly, the people who were on the standard control arm had an ESR1 mutation, we think AIs don't work, they stayed on for nine more months. The patients who were on the camizestrant stayed on for more than 16 months. And they presented some additional subset data which showed the same thing: follow-up PFS data, PFS2, all beneficial in SERENA-6 at the San Antonio [Breast Cancer Symposium]. So, we're still a little bit unclear about that. They did quality of life, and pain was markedly improved. They had a marked delayed time to progression of pain in the camizestrant arm. So this is all a work in progress, trying to understand who should we switch without progression to an oral SERD based on this development of this mutation that correlates with resistance. And, you know, it's interesting because the median time to having a mutation was 18 months and the median time to switch was almost 24 months. And then there were like more than 3,000 patients who hadn't gotten a mutation, hadn't switched, and were still okay. So screening everybody is the big question, and when you would start and who you would change on and how this affects outcome. Patients didn't have access to camizestrant in the control arm, something we can't fix but we have experimental drugs. We're actually planning a trial, I hope in collaboration with the French group Unicancer, and looking at this exact question. You know, if you switch and you change the CDK4/6 inhibitor and then you also allow crossover, what will we see? Dr. Monty Pal: We're coming right to the tail end of our time here, and I could probably go on for another couple of hours with you here. But if you could just give us maybe one or two big highlights from San Antonio, any thoughts to leave our audience with here based on this recent meeting? Dr. Hope Rugo: Yeah, I mean, I talked about a lot of those new data already from San Antonio, and the one that I'd really like to mention which I think was, you know, there were a lot of great presentations including personalized screening presented from the WISDOM trial by my colleague Laura Esserman, fascinating and really a big advance. But lidERA was the big highlight, I think, outside of the HER2CLIMB-05 which I talked about earlier in HER2-positive disease. And this study looked at giredestrant, the oral SERD versus standard of care endocrine therapy as treatment for medium and high-risk early-stage breast cancer. And what they showed, which I think was really remarkable with just about a three-year median follow-up, was an improvement in invasive disease-free survival with a hazard ratio of 0.7. I mean, really quite remarkable and so early. It looked as though this was all driven by the high-risk group, which makes sense, not the medium risk, it's too early. And also that there was a bigger benefit in patients who were on tamoxifen compared to giredestrant versus AI, but for both groups, the confidence intervals didn't cross 1. There's even a trend towards overall survival, even though it's way too early. I think that, you know, really well-tolerated oral drug that could improve outcome in early-stage disease, this is the first advance we've seen in over two decades in the treatment of early-stage hormone receptor-positive disease with just endocrine therapy. I think we think that we don't want to give up CDK4/6 inhibitors because we saw a survival benefit with abemaciclib and a trend with giving ribociclib in the NATALEE trial. So we're thinking that maybe one approach would be to give CDK4/6 inhibitors and then switch to an oral SERD or to have enough data to be able to give oral SERDs with these CDK4/6 inhibitors for early-stage disease. And that's all in the works, you know, lots of studies going on. We're going to see a lot of data with both switching 8,000 patients with an imlunestrant switching trial, an elacestrant trial going on, and safety data with giredestrant with abemaciclib and soon to come ribociclib. So, this is going to change everything for the treatment of early-stage breast cancer, and I hope cure more patients of the most common subset of the most common cancer diagnosed in women worldwide. Dr. Monty Pal: Super exciting. It's just remarkable to hear how this has evolved since 25 years ago, which is really the last time I sort of dabbled in breast cancer.  Thank you so much, Hope, for joining us today. These were fantastic insights. Appreciate you being on the ASCO Daily News Podcast and really want to thank you personally for your remarkable contribution to the field of breast cancer. Dr. Hope Rugo: Thank you very much, and thanks for talking with me today. Dr. Monty Pal: You got it. And thanks a lot to our listeners today as well. You'll find links to all the studies we discussed today in the transcript of this episode. Finally, if you value the insights that you hear today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinion of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:   Dr. Monty Pal @montypal Dr. Hope Rugo   @hoperugo Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:     Dr. Monty Pal:    Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview   Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical   Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx  

In this episode of the Oncology Brothers podcast, we were joined by Dr. Rebecca Shatsky, a breast medical oncologist and director of the Inflammatory and Triple Negative Breast Cancer Program at UC San Diego. We dived into the latest findings from the SABCS 2025 conference, focusing on key studies related to triple negative breast cancer (TNBC). Join us as we discussed: * The RJBC 1501 study, which explored the role of carboplatin in high-risk early-stage TNBC and its impact on disease-free survival. * Insights from the CITRIN study, which questions the carboplatin paradigm and highlights modern treatment approaches. * The TBCRC-056 and OlympiaN trials, investigating the combination of PARP inhibitors and immunotherapy in patients with germline BRCA and PALB2 mutations. We unpacked the implications of these studies for clinical practice, including the potential benefits and challenges of incorporating carboplatin and novel therapies into treatment regimens. Tune in for an informative discussion that aims to keep you updated on the evolving landscape of breast cancer treatment! Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and check out our other episodes for more insights from the world of oncology! #SABCS2025 #TNBC #PARPinhibitors #BRCAmutation #ChemoFree #OncologyBrothers #BreastCancer #SABCS25

At the 2025 San Antonio Breast Cancer Symposium, Justin Johnson, PhD, presented a poster detailing the final results from three groups of people in a phase I trial on a vaccine to prevent triple-negative breast cancer. Listen to the episode to hear Dr. Johnson explain: why the vaccine targets the alpha-lactalbumin protein the safety and dose results of the study what's next for the research

Host: Ryan Quigley Triple-negative breast cancer (TNBC) remains one of the hardest subtypes to treat, with limited options and high relapse rates—so identifying new therapeutic targets is critical. In this AudioAbstract, Ryan Quigley spotlights research presented at the San Antonio Breast Cancer Symposium that implicates ribosome biogenesis as a key vulnerability. Tune in to learn how this approach could inform the next generation of TNBC therapies.

Host: Ryan Quigley Triple-negative breast cancer (TNBC) remains one of the hardest subtypes to treat, with limited options and high relapse rates—so identifying new therapeutic targets is critical. In this AudioAbstract, Ryan Quigley spotlights research presented at the San Antonio Breast Cancer Symposium that implicates ribosome biogenesis as a key vulnerability. Tune in to learn how this approach could inform the next generation of TNBC therapies.

Featuring an interview with Dr Priyanka Sharma, including the following topics: Endocrine therapy for hormone receptor-positive, HER2-negative high-risk localized breast cancer (0:00) Johnston SR et al. monarchE: Primary overall survival (OS) results of adjuvant abemaciclib + endocrine therapy (ET) for HR+, HER2-, high-risk early breast cancer (EBC). ESMO 2025;Abstract LBA13. Durvalumab in combination with neoadjuvant chemotherapy for localized triple-negative breast cancer (TNBC) (3:25) Loibl S et al. Durvalumab in combination with neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC) – Long-term analysis from the GeparNuevo trial. ESMO 2025;Abstract 292MO.  Efficacy and safety findings with TROP2-directed antibody-drug conjugates for metastatic TNBC (5:11) Cortés JC et al. Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i). ESMO 2025;Abstract LBA20.  de Azambuja E et al. Patient-reported outcomes (PROs) with sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in patients (pts) with previously untreated PD-L1+ metastatic triple-negative breast cancer (mTNBC) in the phase III ASCENT-04/KEYNOTE-D19 study. ESMO 2025;Abstract LBA22.  Dent R et al. First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Primary results from the randomised, phase III TROPION-Breast02 trial. ESMO 2025;Abstract LBA21.  CME information and select publications

Lantern Pharma CEO Panna Sharma joined Steve Darling from Proactive to discuss the company's latest clinical milestone and its broader mission to transform oncology drug development through the use of artificial intelligence, machine learning, and genomic data. Lantern's proprietary RADR® AI platform integrates billions of biological and clinical data points to identify predictive biomarkers, forecast drug response, and design more targeted and efficient clinical trials aimed at delivering precision cancer therapies to patients. The company announced additional details from its recently completed Phase 1a dose-escalation study of LP-184, its lead drug candidate. The trial produced encouraging results, demonstrating durable disease control in 63 heavily pre-treated patients with advanced solid tumors, many of which exhibited deficiencies in DNA damage repair pathways—an area where LP-184 is designed to be particularly effective. Sharma told Proactive that the Phase 1a study successfully met all primary endpoints for safety and tolerability, while also clearly establishing a recommended Phase 2 dose (RP2D). He emphasized that these outcomes validate both the scientific rationale behind LP-184 and the predictive capabilities of Lantern's AI-driven development approach. Building on these positive results, Lantern Pharma is now advancing an ambitious precision oncology strategy that includes multiple biomarker-guided Phase 1b/2 clinical trials. These studies will target major cancer indications such as triple-negative breast cancer (TNBC), glioblastoma multiforme (GBM), non-small cell lung cancer, and advanced bladder cancer. The commercial potential for LP-184 is significant. Lantern and independent industry analysts estimate that the aggregate annual market opportunity for the drug across these and additional targeted indications could exceed $10 billion. Preclinical models have shown nanomolar potency, while early clinical data indicate encouraging durability of response even in heavily pre-treated patient populations. LP-184 has also received important regulatory recognition from the U.S. Food and Drug Administration, including Fast Track Designation for TNBC and GBM, as well as Orphan Drug Designation for malignant gliomas, pancreatic cancer, and atypical teratoid/rhabdoid tumors (ATRT). Sharma noted that these designations support an accelerated development pathway as Lantern continues to move LP-184 toward later-stage clinical trials. #proactiveinvestors #laternpharma #nasdaq #ltrn #LanternPharma #PannaSharma #PrecisionOncology #CancerResearch #AIinHealthcare #MachineLearning #Genomics #ClinicalTrials #BiotechNews #OncologyInnovation #LP184 #Phase1a #Phase2Trials #BiomarkerDriven #TripleNegativeBreastCancer #Glioblastoma #LungCancer #BladderCancer #OrphanDrug #FastTrackDesignation #FDA #PrecisionMedicine

Dr. Andrei Goga and his colleagues found that triple-negative breast cancer cells build molecular tunnels called gap junctions into nearby fat cells and use the fat cells' energy for fuel. When the scientists blocked the gap junctions, the tumors stopped growing. Listen to the episode to hear Dr. Goga explain: how the study came about how the cancer cells connect to the fat cells how the process could work in metastatic TNBC what the results could mean for treating triple negative disease.

Dr. Jay Lalezari, CEO of CytoDyn, is focused on solid tumor immunology, particularly in triple-negative breast cancer, where their lead drug, leronlimab, is showing significant long-term survival benefits.  This monoclonal antibody targets the CCR5 receptor, converting cold tumors into hot tumors and making them more susceptible to immunotherapy checkpoint inhibitors. Work with leronlimab for 20 years has demonstrated the potential for use in colorectal cancer as well as TNBC, and to vastly expand the patient population that could benefit from immunotherapy. Jay explains, "When I became CEO back in November of 2023, my first order of business was to figure out where CytoDyn should go with this intriguing monoclonal antibody called leronlimab that targets CCR5. And we looked at a number of indications, and by far and away, the data that we found in solid tumor oncology is clearly the place CytoDyn will go to create the most benefit for patients and the most benefit for our shareholders. We recently presented some data in triple-negative breast cancer that is truly remarkable and potentially paradigm-shifting in the world of solid tumor oncology."   "Over the years, it became clear that CCR5 was not just for the virus to get inside the cell, but was playing a key role in setting up the tumor microenvironment in a variety of solid tumors that were CCR5 positive. That included typically triple-negative breast cancer, colon cancer, prostate cancer, pancreatic cancer, sarcoma, glioblastoma, and the urothelial cancers in particular. So CCR5 helps the cancer set up a tumor microenvironment that helps it both build blood vessels to provide nourishment for the cancer and attract suppressor cells that keep the host immune system at bay."  #CytoDyn #Oncology #Leronlimab #TNBC #ColorectalCancer #CCR5 cytodyn.com Listen to the podcast here

Dr. Jay Lalezari, CEO of CytoDyn, is focused on solid tumor immunology, particularly in triple-negative breast cancer, where their lead drug, leronlimab, is showing significant long-term survival benefits.  This monoclonal antibody targets the CCR5 receptor, converting cold tumors into hot tumors and making them more susceptible to immunotherapy checkpoint inhibitors. Work with leronlimab for 20 years has demonstrated the potential for use in colorectal cancer as well as TNBC, and to vastly expand the patient population that could benefit from immunotherapy. Jay explains, "When I became CEO back in November of 2023, my first order of business was to figure out where CytoDyn should go with this intriguing monoclonal antibody called leronlimab that targets CCR5. And we looked at a number of indications, and by far and away, the data that we found in solid tumor oncology is clearly the place CytoDyn will go to create the most benefit for patients and the most benefit for our shareholders. We recently presented some data in triple-negative breast cancer that is truly remarkable and potentially paradigm-shifting in the world of solid tumor oncology."   "Over the years, it became clear that CCR5 was not just for the virus to get inside the cell, but was playing a key role in setting up the tumor microenvironment in a variety of solid tumors that were CCR5 positive. That included typically triple-negative breast cancer, colon cancer, prostate cancer, pancreatic cancer, sarcoma, glioblastoma, and the urothelial cancers in particular. So CCR5 helps the cancer set up a tumor microenvironment that helps it both build blood vessels to provide nourishment for the cancer and attract suppressor cells that keep the host immune system at bay."  #CytoDyn #Oncology #Leronlimab #TNBC #ColorectalCancer #CCR5 cytodyn.com Download the transcript here

Janice Cowden, retired nurse and patient advocate, shares her remarkable triple negative breast cancer (TNBC) story. Five years following successful treatment for stage one breast cancer in 2011, Janice was diagnosed with a stage 4 metastatic TNBC recurrence. As of today she has 8 years of no evidence of disease (NED) under her belt. She shares how she stumbled upon the cancer community that inspired her to become the advocate she is today and the uncertainty that comes with NED. She also shares how she copes with losing friends in the cancer community through her patient advocacy work. We also have a rapid fire Q&A where she answers questions surrounding various medical terminologies, diagnoses, and more to keep you in the loop. NOTE: There is one clarification from the rapid fire Q&A session. The definition of disease free survival (DFS) is the time from random assignment (used in clinical trials and research studies to assign participants to different groups) to cancer recurrence or death from any cause (Gutman SI, Piper M, Grant MD, et al. 2013).Key Highlights:1. Metastatic breast cancer (MBC) is stage four breast cancer that has spread to distant sites in the body.2. Finding events and communities centered around cancer not only supports cancer patients emotionally and socially, but can also serve as informational hubs. Being proactive in learning about your diagnosis, whether it's through community and/or research on your own time, can help you feel confident with the choices you make. 3. While finding a community of other cancer patients can help, unfortunately this disease means that you will lose friends you make in these settings. It doesn't necessarily get easier, but finding an outlet to cope with such losses is vital to your wellbeing.About our guest:Diagnosed with Stage IV triple negative breast cancer in 2016, five years after an early-stage breast cancer diagnosis, Janice launched into patient advocacy following training through Living Beyond Breast Cancer's (LBBC) Hear My Voice Outreach program in 2017. As a peer-to-peer support and research patient advocate, Janice is passionate about supporting others with metastatic breast cancer, in addition to continually furthering her scientific knowledge base of this disease, treatments, and clinical trials, which she acquires through attending scientific breast cancer conferences and webinars. Janice is involved with several patient-founded and led organizations including PCDI, GRASP, and Project Life MBC. As a trained peer support volunteer, she is founder of an international online peer support group for patients newly diagnosed with MBC. She serves on the Board of Directors for METAvivor Research and Support Inc., and is an Advisory Board member for Project Life MBC. She is an individual member of the Metastatic Breast Cancer Alliance. When she's not busy with advocacy work, Janice enjoys traveling, reading, outdoor activities, and spending time with family, including her husband, two adult children and three grandchildren.Disclaimer: This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this podcast or materials linked from this podcast is at the user's own risk. The content of this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.

This is a bonus episode of the audio of a Breastcancer.org ⁠⁠⁠⁠webinar⁠⁠⁠⁠. Triple-negative breast cancer (TNBC) is an invasive subtype of breast cancer that can be harder to treat and is more likely to come back. But new research into understanding TNBC is helping some patients find more precise treatment options.  Learn about innovations in immunotherapy, genetic testing, and targeted therapies, why TNBC is different compared to other types of breast cancer, and what gives doctors hope about the future of care for people with TNBC. You'll also hear from two inspiring breast cancer advocates who created TNBC resources for patients after their own diagnosis. Read more about triple-negative breast cancer. Featured Speakers: Maimah KarmoBreast Cancer Advocate and Founder, Tigerlily Roberto Leon-Ferre, MDCo-Leader of the Triple-Negative Breast Cancer Working Group and Associate Professor at Mayo Clinic Evelyn Taiwo, MDHematology and Oncology at New York Presbyterian Brooklyn Methodist Hospital and Associate Professor at Cornell University Kelly ThomasBreast Cancer Advocate and Founder, TNBC Thrivers Marisa Weiss, MDChief Medical Officer, Breastcancer.org

Triple-negative breast cancer is negative for both estrogen and progesterone receptors. So, it's hormone receptor-negative. People diagnosed with this type of breast cancer aren't offered hormonal therapy to reduce the risk of recurrence (the cancer coming back) because it's thought that they wouldn't be effective.  Dr. Lisa Newman and colleagues published research that found that among people diagnosed with early-stage triple-negative breast cancer, nearly 33% of the recurrences or second primary breast cancers were hormone receptor-positive. This means the hormone receptor status had changed when the cancer came back or when there was a new cancer. The results raise this question: Should people with triple-negative disease be offered hormonal therapy to reduce the risk of recurrence? Listen to the episode to hear Dr. Newman explain: how she decided to investigate this issue why the results surprised her what the results mean for someone who's been diagnosed with triple-negative breast cancer with a high risk of recurrence

Featuring perspectives from Dr Ana C Garrido-Castro and Prof Peter Schmid, including the following topics:  Introduction: Legendary Figures in Breast Cancer Research (0:00) Case: A woman in her early 80s, a current smoker with a history of myocardial infarction and stroke, who develops recurrent triple-negative breast cancer (TNBC) — Justin Favaro, MD, PhD (6:44) Case: A woman in her late 60s with metastatic TNBC and a PD-L1 level of 20% who receives chemotherapy/pembrolizumab followed by sacituzumab govitecan — Priya Rudolph, MD, PhD (25:08) Case: A woman in her late 60s with localized TNBC who develops myocarditis while receiving neoadjuvant chemotherapy/pembrolizumab — Richard Zelkowitz, MD (33:53) Case: A woman in her mid 60s with recurrent ER-negative, HER2-low, PI3K-mutant TNBC — Ranju Gupta, MD (37:49) Case: A woman in her early 60s with recurrent TNBC confined to contralateral neck nodes — Eric H Lee, MD, PhD (42:10) Case: A woman in her early 40s with metastatic TNBC who receives sacituzumab govitecan after multiple lines of chemotherapy — Estelamari Rodriguez, MD, MPH (48:10) Case: A woman in her mid 70s with ER-negative, HER2-low breast cancer who develops an isolated brain metastasis — Dr Gupta (55:02) CME information and select publications

In this podcast, experts Virginia Kaklamani, MD, DSc, and Tiffany A. Traina, MD, FASCO, discuss the rationale for and data to support combining TROP2-targeting antibody-drug conjugates (ADCs) with immune checkpoint inhibitors (ICIs) to treat triple-negative breast cancer (TNBC).

In this podcast, experts Aditya Bardia, MD, MPH, FASCO, Erika P. Hamilton, MD, and Virginia Kaklamani, MD, DSc, discuss frequently asked questions regarding the use of antibody-drug conjugates (ADCs) in triple-negative breast cancer (TNBC).

In this podcast, experts Filipa Lynce, MD, and Rita Nanda, MD, discuss recent clinical trial and real-world data for antibody-drug conjugates (ADCs) used to treat triple-negative breast cancer (TNBC).

In this podcast, experts Aditya Bardia, MD, MPH, FASCO; Erika P. Hamilton, MD; and Tiffany A. Traina, MD, FASCO; discuss navigating between currently available therapies for patients with triple-negative breast cancer (TNBC). They also discuss the potential ramifications of ongoing clinical trials on future treatment paradigms.

In this podcast, experts Filipa Lynce, MD, and Rita Nanda, MD, discuss unmet needs in triple-negative breast cancer (TNBC) and the rationale for using TROP2-targeting antibody-drug conjugates (ADCs) in this disease.

In this podcast, experts Aditya Bardia, MD, MPH, FASCO; and Erika P. Hamilton, MD, discuss recent efficacy and safety data of TROP2-targeted antibody-drug conjugate (ADC) plus immune checkpoint inhibitor combinations for advanced triple-negative breast cancer (TNBC).

Dr. Allison Zibelli and Dr. Rebecca Shatsky discuss advances in breast cancer research that were presented at the 2025 ASCO Annual Meeting, including a potential new standard of care for HER2+ breast cancer, the future of ER+ breast cancer management, and innovations in triple negative breast cancer therapy. Transcript Dr. Allison Zibelli: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Allison Zibelli, your guest host of the podcast today. I'm an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Comprehensive Cancer Center at Jefferson Health. There was a substantial amount of exciting breast cancer data presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Rebecca Shatsky today to discuss some of these key advancements. Dr. Shatsky is an associate professor of medicine at UC San Diego and the head of breast medical oncology at the UC San Diego Health Moores Cancer Center, where she also serves as the director of the Breast Cancer Clinical Trials Program and the Inflammatory and Triple-Negative Breast Cancer Program.  Our full disclosures are available in the transcript of this episode. Dr. Shatsky, it's great to have you on the podcast today. Dr. Rebecca Shatsky: Thanks, Dr. Zibelli. It's wonderful to be here. Dr. Allison Zibelli: So, we're starting with DESTINY-Breast09, which was trastuzumab deruxtecan and pertuzumab versus our more standard regimen of taxane, trastuzumab pertuzumab for first-line treatment of metastatic HER2-positive breast cancer. Could you tell us a little bit about the study? Dr. Rebecca Shatsky: Yeah, absolutely. So, this was a long-awaited study. When T-DXd, or trastuzumab deruxtecan, really hit the market, a lot of these DESTINY-Breast trials were started around the same time. Now, this was a global, randomized, phase 3 study presented by Dr. Sara Tolaney from the Dana-Farber Cancer Institute of Harvard in Boston. It was assessing essentially T-DXd in the first-line setting for metastatic HER2-positive breast cancer in addition to pertuzumab. And that was randomized against our standard-of-care regimen, which was established over a decade ago by the CLEOPATRA trial, and we've all been using that internationally for at least the past 10 years. So, this was a large trial, and it was one-to-one-to-one of patients getting T-DXd plus pertuzumab, T-DXd alone, or THP, which mostly is used as docetaxel and trastuzumab and pertuzumab every three weeks for six cycles. And this was in over 1,000 patients; it was 1,159 patients with metastatic HER2-positive breast cancer. This was a very interesting trial. It was looking at the use of trastuzumab deruxtecan, but patients were started on this treatment for their first-line metastatic HER2-positive breast cancer with no end date to their T-DXd. So, it was, you know, you were started on T-DXd every 3 weeks until progression. Now, CLEOPATRA is a little bit different than that, though, as we know. So, CLEOPATRA has a taxane plus trastuzumab and pertuzumab. But generally, patients drop the taxane after about six to seven cycles because, as we know, you can't be really on a taxane indefinitely. You get pretty substantial neuropathy as well as cytopenias, other things that end up happening. And so, in general, that regimen has sort of a limited time course for its chemotherapy portion, and the patients maintained after the taxane is dropped on their trastuzumab and their pertuzumab, plus or minus endocrine therapy if the investigator so desires. And the primary endpoint of the trial was progression-free survival by blinded, independent central review (BICR) in the intent-to-treat population. And then it had its other endpoints as overall survival, investigator-assessed progression-free survival, objective response rates, and duration of response, and of course, safety. As far as the results of this trial, so, I think that most of us key opinion leaders in breast oncology were expecting that this was going to be a positive trial. And it surely was. I mean, this is a really, really active drug, especially in HER2-positive disease, of course. So, the DESTINY-Breast03 data really established that, that this is a very effective treatment in HER2-positive metastatic breast cancer. And this trial really, again, showed that. So, there were 383 patients that ended up on the trastuzumab plus deruxtecan plus pertuzumab arm, and 387 got THP, the CLEOPATRA regimen. What was really interesting also to note of this before I go on to the results was that 52% of patients on this trial had de novo metastatic disease. And that's pretty unusual for any kind of metastatic breast cancer trial. It kind of shows you, though, just how aggressive this disease is, that a lot of patients, they present with de novo metastatic disease. It's also reflecting the global nature of this trial where maybe the screening efforts are a little bit less than maybe in the United States, and more patients are presenting as later stage because to have a metastatic breast cancer trial in the United States with 52% de novo metastatic disease doesn't usually happen. But regardless, the disease characteristics were pretty well matched between the two groups. 54% of the patients were triple positive, or you could say hormone-positive because whether they were PR positive or ER positive and PR negative doesn't really matter in this disease. And so, the interim data cutoff was February of this year, of 2025. So, the follow-up so far has been about 29 months, so the data is still really immature, only 38% mature for progression-free survival interim analysis. But what we saw is that T-DXd plus pertuzumab, it really improved progression-free survival. It had a hazard ratio that was pretty phenomenal at 0.56 with a confidence interval that was pretty narrow of 0.44 to 0.71. So, very highly statistically significant data here. The progression-free survival was consistent across all subgroups. Overall survival, very much immature at this time, but of course, the trend is towards an overall survival benefit for the T-DXd group. The median durable response with T-DXd plus pertuzumab exceeded 3 years. Now, importantly, though, I want to stress this, is grade 3 or above treatment-emergent adverse events occurred in both subgroups pretty equally. But there were 2 deaths in the T-DXd group due to interstitial lung disease. And there was a 12.1% adjudicated drug-induced interstitial lung disease/pneumonitis event rate in the T-DXd group and only 1%, and it was grade 1-2, in the THP group. So, that's really the caveat of this therapy, is we know that a percentage of patients are going to get interstitial lung disease, and that some may have very serious adverse events from it. So, that's always something I keep in the back of my mind when I treat patients with T-DXd. And so, overall, the conclusions of the trial were pretty much a slam dunk. T-DXd plus pertuzumab, it had a highly statistically significant and clinically meaningful improvement in progression-free survival versus the CLEOPATRA regimen. And that was across all subgroups for first-line metastatic HER2-positive breast cancer here. And so, yeah, the data was pretty impressive. Just to go into the overall response rate, because that's always super important as well, you had 85.1% of patients having a confirmed overall RECIST response rate in the T-DXd plus pertuzumab group and a 78.6 in the CLEOPATRA group. The complete CR rate, complete response was 15.1% in the T-DXd group and 8.5 in the CLEOPATRA regimen. And it was really an effective regimen in this group, of course. Dr. Allison Zibelli: So, the investigators say at the end of their abstract that this is the new standard of care. Would you agree with that statement? Dr. Rebecca Shatsky: Yeah, that was a bold statement to make because I would say in the United States, not necessarily at the moment because the quality of life here, you have to think really hard about. Because one thing that's really important about the DESTINY-Breast09 data is that this was very much an international trial, and in many of the countries where patients enrolled on this, they were not able to access T-DXd off trial. And so, for them, this means T-DXd now or potentially never. And so, that is a really big difference whereas internationally, that may mean standard of care. However, in the US, patients have no issues accessing T-DXd in the second- or third-line settings. And right now, it's the standard of care in the second line in the United States, with all patients basically getting this second-line therapy except for some unique patients where they may be doing a PATINA trial regimen, which we saw at San Antonio Breast Cancer in 2024 of the triple-positive patients getting hormonal therapy plus palbociclib, which had a really great durable response. That was super impressive as well. Or there is the patient that the investigator can pick KADCYLA because the patient really wants to preserve their hair or maybe it's more indolent disease. But the quality of life on T-DXd indefinitely in the first-line setting is a big deal because, again, that CLEOPATRA regimen allows patients to drop their chemotherapy component about five to six months in. And with this, you're on a drug that feels very chemo-heavy indefinitely. And so, I think there's a lot more to investigate as far as what we're going to do with this data in the United States because it's a lot to commit a patient in the first-line metastatic setting. These de novo metastatic patients, some of them may be cured, honestly, on the HER2-targeting regimen. That's something we see these days. Dr. Allison Zibelli: So, very interesting trial. I'm sure we'll be talking about this for a long time.  So, let's move on to SERENA-6, which was, I thought, a very interesting trial. This trial took patients with ER positive, advanced breast cancer after six months on an AI (aromatase inhibitor) and a CDK4/6 inhibitor. They did ctDNA every two to three months, and when they saw an ESR1 mutation emerge, they changed half of the patients to camizestrant plus CDK4/6 and kept the other half on the AI plus CDK4/6. Can you talk about that trial a little bit, please? Dr. Rebecca Shatsky: Yeah, so this was a big trial at ASCO25. This was presented as a Plenary Session. So, this was camizestrant plus a CDK4/6 inhibitor, and it could have been any of the three, so palbo, ribo, or abemaciclib in the first-line metastatic hormone-positive population, and patients were on an AI with that. They were, interestingly, tested by ctDNA at baseline to see if they had an ESR1 mutation. So, that was an interesting feature of this trial. But patients had to have already been on their CDK4/6 inhibitor plus AI for at least 6 months to enroll. And then, as you mentioned, they got ctDNA testing every 2 to 3 months. This was also a phase 3, double-blind, international trial. And I do want to highlight again, international here, because that's important when we're considering some of this data in the U.S. because it influences some of the results. So, this was presented by Dr. Nick Turner of the Royal Marsden in the UK. So, just a little bit of background for our listeners on ESR1 mutations and why they're important. This is the most common, basically, acquired resistance mutation to patients being treated with aromatase inhibitors. We know that treatment with aromatase inhibitors can induce this. It makes a conformational change in the estrogen receptor that makes the estrogen receptor constitutively active, which allows the cell to signal despite the influence of the aromatase inhibitor to decrease the estrogen production so that the ligand binding doesn't matter as much as far as the cell signaling and transcription is concerned. And camizestrant, you know, as an oral SERD, just to explain that a little bit too; these are estrogen receptor degraders. The first-in-class of a selective estrogen receptor degrader to make it to market was fulvestrant. And that's really been our standard-of-care estrogen degrader for the past 25 years, almost 25 years. And so, a lot of us are just looking for some of these oral SERDs to replace that. But regardless, they do tend to work in the ESR1-mutated population. And we know that patients on aromatase inhibitors, the estimates of patients developing an ESR1 mutation, depending on which study you look at, somewhere between 30% to 50% overall, patients will develop this mutation with hormone-positive metastatic breast cancer. There is a small percentage of patients that have these at baseline without even treatment of an aromatase inhibitor. The estimates of that are somewhere between 0.5 and up to 5%, depending on the trial you look at and the population. But regardless, there is a chance someone on their CDK4/6 inhibitor plus AI at 6 months' time course could have had an ESR1 mutation at that time. But anyway, so they got this ctDNA every 2 to 3 months, and once they were found to develop an ESR1 mutation, the patients were then switched to the oral SERD. AstraZeneca's version of the oral SERD is camizestrant, 75 mg daily. And then their type of CDK4/6 inhibitor was maintained, so they didn't switch the brand of their CDK4/6 inhibitor, importantly. And that was looked at then for progression-free survival, but these were patients with measurable disease by RECIST version 1.1. And the data cut off here was November of 2024. This was a big trial, you know, and I think that that's influential here because this was 3,256 patients, and that's a lot of patients. So, they were all eligible. And then 315 patients ended up being randomized to switch to camizestrant upon presence of that ESR1 mutation. So, that was 157 patients. And then the other half, so they were randomized 1:1, they continued on their AI without switching to an oral SERD. That was 158 patients. They were matched pretty well. And so, their baseline characteristics, you know, the two subgroups was good. But this was highly statistically significant data. I'm not going to diminish that in any way. Your hazard ratio was 0.44. Highly statistically significant confidence intervals. And you had a median progression-free survival in those that switched to camizestrant of 16 months, and then the non-switchers was 9.2 months. So, the progression-free survival benefit there was also consistent across the subgroups. And so, you had at 12 months, the PFS rate was 60.7% for the non-treatment group and 33.4% in the treatment group. What's interesting, though, is we don't have overall survival data. This is really immature, only 12% mature as far as overall survival. And again, because this was an international trial and patients in other countries right now do not have the access to oral SERDs that the United States does, the crossover rate, they were not allowed to crossover, and so, a very few patients, when we look at progression-free survival 2 and ultimately overall survival, were able to access an oral SERD in the off-trial here and in the non-treatment group. And so, that's really important as far as we look at these results. Adverse events were pretty minimal. These are very safe drugs, camizestrant and all the other oral SERDs. They have some mild toxicities. Camizestrant is known for something weird, which is called photopsia, which is some flashing lights in the periphery of the eye, but it doesn't seem to have any serious clinical significance that we know of. It has a little bit of bradycardia, but it's otherwise really well tolerated. You know, I hate to say that because that's very subjective, right? I'm not the one taking the drug. But it doesn't have any serious adverse events that would cause discontinuation. And that's really what we saw in the trial. The discontinuation rates were really low. But overall, I mean, this was a positive trial. SERENA-6 showed that switching to camizestrant at the first sign of an ESR1 mutation on CDK4/6 inhibitor plus AI improved progression-free survival. That's all we can really say from it right now. Dr. Allison Zibelli: So, let's move on to ASCENT-04, which was a bit more straightforward. Sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab in PD-L1-positive, triple-negative breast cancer. Could you talk about that study? Dr. Rebecca Shatsky: Yeah, so this was also presented by the lovely Sara Tolaney from Dana-Farber. And this study made me really excited. And maybe that's because I'm a triple-negative breast cancer person. I mean, not to say that I don't treat hundreds of patients with hormone- positive, but our unmet needs in triple negative are huge because this is a disease where you have got to throw your best available therapy at it as soon as you can to improve survival because survival is so poor in this disease. The average survival with metastatic triple-negative breast cancer in the United States is still 13-18 months, and that's terrible. And so, for full disclosure, I did have this trial open at my site. I was one of the site PIs. I'm not the global PI of the study, obviously. So, what this study was was for patients who had had at least a progression-free survival of 6 months after their curative intent therapy or de novo metastatic disease. They were PD-L1 positive as assessed by the Dako 22C3 assay of greater than or equal to a CPS score of 10. So, that's what the KEYNOTE-355 trial was based on as well. So, standard definition of PD-L1 positive in breast cancer here. And basically, these patients were randomized 1:1 to either their sacituzumab govitecan plus pembrolizumab, day 1 they got both therapies, and then day 8 just the saci, as is standard for sacituzumab. And then the other group got the KEYNOTE-355 regimen. So, that is pembrolizumab with – your options are carbogem there, paclitaxel or nab-paclitaxel. And it's up to investigator's decision which upon those they decided. They followed these patients for disease progression or unacceptable toxicity. It was really an impressive trial in my opinion because we know already that this didn't just improve progression-free survival, because survival is so poor in this disease, of course, we know that it improved overall survival. It's trending towards that very much, and I think that's going to be shown immediately. And then the objective response rates were better, which is key in this disease because in the first-line setting, you've got a lot of people who, especially your relapsed TNBC that don't respond to anything. And you lose a ton of patients even in the first-line setting in this disease. And so, this was 222 patients to chemotherapy and pembro and 221 to sacituzumab plus pembro. Median follow-up has only been 14 months, so it's still super early here. Hazard ratio so far of progression-free survival is 0.65, highly statistically significant, narrow confidence intervals. And so, the median duration of response here for the saci group was 16.5 months versus 9.2 months. So, you're getting a 7-month progression-free survival benefit here, which in triple negative is pretty fantastic. I mean, this reminds me of when we saw the ASCENT data originally come out for sacituzumab, and we were all just so happy that we had this tool now that doubled progression-free and overall survival and made such a difference in this really horrible disease where patients do poorly. So, OS is technically immature here, but it's really trending very heavily towards improvement in overall survival. Importantly, the treatment-related adverse events in this, I mean, we know sacituzumab causes neutropenia, people who are experienced with this drug know how to manage it at this point. There wasn't any really unexpected treatment-related adverse events. You get some people with sacituzumab who have diarrhea. It's usually pretty manageable with some Imodium. So, it was cytopenias predominantly in this disease in this population that were highlighted as far as adverse events. But I'm going to be honest, like I was surprised that this wasn't the plenary over the SERENA-6 data because this, in my mind, there we have a practice-changing trial. I will immediately be trying to use this in my PD-L1 population because, to be honest, as a triple-negative breast cancer clinical specialist, when I get a patient with metastatic triple-negative breast cancer who's PD-L1 positive, I think, "Oh, thank God," because we know that part of the disease just does better in general. But now I have something that really could give them a durable response for much longer than I ever thought possible when I started really heavily treating this disease. And so, this was immediately practice-changing for me. Dr. Allison Zibelli: I think that it's pretty clear that this is at least an option, if not the option, for this group of patients. Dr. Rebecca Shatsky: Yeah, the duration of responses here was – it's just really important because, I mean, I do think this will make people live longer. Dr. Allison Zibelli: So, moving on to the final study that we're going to discuss today, neoCARHP (LBA500), which was neoadjuvant taxane plus trastuzumab, pertuzumab, plus or minus carbo(platin) in HER2-positive early breast cancer. I think this is a study a lot of us have been waiting for. What was the design and the results of this trial? Dr. Rebecca Shatsky: I was really excited about this as well because I'm one of those people that was waiting for this. This is a Chinese trial, so that is something to take note of. It wasn't an international trial, but it was a de-escalation trial which had become really popular in HER2-positive therapy because we know that we're overtreating HER2-positive breast cancer in a lot of patients. A lot of patients we're throwing the kitchen sink at it when maybe that is not necessary, and we can really de-escalate and try to personalize therapy a little bit better because these patients tend to do well. So, the standard of care, of course, in HER2-positive curative intent breast cancer with tumors that are greater than 2 cm is to give them the TCHP regimen, which is docetaxel, carboplatin, trastuzumab, and pertuzumab. And that was sort of established by several trials in the NeoSphere trial, and now it's been repeated in a lot of different studies as well. And so, that's really the standard of care that most people in the United States use for HER2-positive curative intent breast cancer. This was a trial to de-escalate the carboplatin, which I was super excited about because many of us who treat this disease a lot think carbo is the least important part of the therapy you're giving there. We don't really know that it's necessary. We've just been doing it for a long time, and we know that it adds a significant amount of toxicity. It causes thrombocytopenia, it causes severe nausea, really bad cytopenias that can be difficult in the last few cycles of this to manage. So, this trial was created. It randomized patients one to one with stage 2 and 3 HER2-positive breast cancer to either get THP, a taxane, pertuzumab, trastuzumab, similar to the what we do in first-line metastatic HER2-positive versus the whole TCHP with a carboplatin AUC of 6, which is what's pretty standard. And it was a non-inferiority trial, so important there. It wasn't to establish superiority of this regimen, which none of us, I think, were looking for it to. And it was a modified intent-to-treat population. And so, all patients got at least one cycle of this to be assessed as a standard for an intent-to-treat trial. And so, they assumed a pCR rate of about 62.8% for both groups. And, of course, it included both HER2-positive triple positives and ER negatives, which are, you know, a bit different diseases, to be honest, but we all kind of categorize them and treat them the same. And so, this trial was powered appropriately to detect a non-inferiority difference. And so, we had about 380 patients treated on both arms, and there was an absolute difference of only 1.8% of those treated with carbo versus those without. Which was fantastic because you really realized that de-escalation here may be something we can really do. And so, the patients who got, of course, the taxane regimen had fewer adverse events. They had way fewer grade 3 and 4 adverse events than the THP group. No treatment-associated deaths occur, which is pretty standard for- this is a pretty safe regimen, but it causes a lot of hospitalizations due to diarrhea, due to cytopenias, and neutropenic fever, of course. And so, I thought that this was something that I could potentially enact, you know, and be practice-changing. It's hard to say that when it's a trial that was only done in China, so it's not necessarily the United States population always. But I think for patients moving forward, especially those with, say, a 2.5 cm tumor, you know, node negative, those, I'd feel pretty comfortable not giving them the carboplatin here. Notes that I want to make about this population is that the majority were stage 2 and not stage 3. They weren't necessarily your inflammatory HER2-positive breast cancer patients. And that the taxane that was utilized in the trial is a little different than what we use in the United States. The patients were allowed to get nab-paclitaxel, which we don't have FDA approval for in the first-line curative intent setting for HER2-positive breast cancer in the United States. So, a lot of them got abraxane, and then they also got paclitaxel. We tend to use docetaxel every 3 weeks in the United States. So, just to point out that difference. We don't really know if that's important or not, but it's just a little bit different to the population we standardly treat. Dr. Allison Zibelli: So, are there patients that you would still give TCHP to? Dr. Rebecca Shatsky: Yeah, great question. I've been asked that a lot in the past like week since ASCO. I'd say in my inflammatory breast cancer patients, that's a group I do tend to sometimes throw the kitchen sink at. Now, I don't actually use AC in those because I know that that was the concern, but I think the TRAIN-2 trial really showed us you don't need to use Adriamycin in HER2-positive disease unless it's like refractory. So, I don't know that I would throw this on my stage 3C or inflammatory breast cancer patients yet because the majority of this were not stage 3. So, in your really highly lymph node positive patients, I'm a little bit hesitant to de-escalate them from the start. This is more of a like, if there's serious toxicity concerns, dropping carbo is absolutely fine here. Dr. Allison Zibelli: All right, great.  Thank you, Dr. Shatsky, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Rebecca Shatsky: Thanks so much, Dr. Zibelli and ASCO Daily News. I really want to thank you for inviting me to talk about this today. It was really fun, and I hope you find my opinions on some of this valuable. And so, I just want to thank everybody and my listeners as well. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you learn things from it, please take a moment to rate, review, and describe because it helps other people find us wherever you get your podcasts. Thank you again. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers Dr. Allison Zibelli Dr. Rebecca Shatsky @Dr_RShatsky Follow ASCO on social media:  @ASCO on Twitter  @ASCO on Bluesky  ASCO on Facebook  ASCO on LinkedIn   Disclosures: Dr. Allison Zibelli: No relationships to disclose Dr. Rebecca Shatsky: Consulting or Advisory Role: Stemline, Astra Zeneca, Endeavor BioMedicines, Lilly, Novartis, TEMPUS, Guardant Health, Daiichi Sankyo/Astra Zeneca, Pfizer Research Funding (Inst.): OBI Pharma, Astra Zeneca, Greenwich LifeSciences, Briacell, Gilead, OnKure, QuantumLeap Health, Stemline Therapeutics, Regor Therapeutics, Greenwich LifeSciences, Alterome Therapeutics  

Peter Schmid, FRCP, MD, PhD - Use of Neoadjuvant Chemoimmunotherapy Followed by Adjuvant Immunotherapy in Early-Stage TNBC: A Case-Based Discussion

This week on the M3P Podcast, Evo and Gregg dive deep into nostalgia with Evo's latest nerd haul, All-Star Superman, and Marvel Rivals' new season. But the heart of this episode is pure 90s gold: we're talking favorite TGIF lineups, Saturday morning teen shows, Mom's summer cleaning soundtrack (was it R&B or salsa?), iconic telenovelas, and how many times we snuck into the movie theater to rewatch our favorite summer blockbusters.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA information, and to apply for credit, please visit us at PeerView.com/QJY865. CME/MOC/NCPD/AAPA credit will be available until May 13, 2026.Navigating the Clinical Integration of TROP2-Targeted ADCs in TNBC and HR+, HER2- Metastatic Breast Cancer: A Customized Learning Journey In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA information, and to apply for credit, please visit us at PeerView.com/QJY865. CME/MOC/NCPD/AAPA credit will be available until May 13, 2026.Navigating the Clinical Integration of TROP2-Targeted ADCs in TNBC and HR+, HER2- Metastatic Breast Cancer: A Customized Learning Journey In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA information, and to apply for credit, please visit us at PeerView.com/QJY865. CME/MOC/NCPD/AAPA credit will be available until May 13, 2026.Navigating the Clinical Integration of TROP2-Targeted ADCs in TNBC and HR+, HER2- Metastatic Breast Cancer: A Customized Learning Journey In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA information, and to apply for credit, please visit us at PeerView.com/QJY865. CME/MOC/NCPD/AAPA credit will be available until May 13, 2026.Navigating the Clinical Integration of TROP2-Targeted ADCs in TNBC and HR+, HER2- Metastatic Breast Cancer: A Customized Learning Journey In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis program has been supported by an independent educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

Danielle studies triple-negative breast cancer (TNBC), an aggressive breast cancer subtype associated with poor survival. Unlike other subtypes for which there are targeted therapies, treatment options for TNBC are limited. In order to better understand the biology underlying TNBC, she studies a family of proteins called calpains. For upcoming interviews check out the Grad Chat webpage on Queen’s University School of Graduate Studies & Postdoctoral Affairs website.

Featuring a slide presentation and related discussion from Dr Adrienne G Waks, including the following topics: Updated analyses from key studies of the 21-gene Recurrence Score® for localized ER-positive breast cancer (29:30) Four-year landmark analysis of the NATALEE trial of adjuvant ribociclib with nonsteroidal aromatase inhibitor for localized breast cancer (9:49) The PADMA trial of palbociclib with endocrine therapy compared to chemotherapy induction followed by endocrine therapy maintenance for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC) (11:25) Imlunestrant with or without abemaciclib for metastatic ER-positive mBC (13:18) TROP2-directed antibody-drug conjugates (ADCs) datopotamab deruxtecan and sacituzumab tirumotecan for HR-positive/HER2-negative mBC (17:50) Recent analyses from the DESTINY-Breast06 trial of trastuzumab deruxtecan (T-DXd) after endocrine therapy for HR-positive, HER2-low or HER2-ultralow mBC (21:09) The ICARUS-BREAST01 Phase II trial of the HER3-targeted ADC patritumab deruxtecan for HR-positive/HER2-negative mBC (26:02) Updates from neoadjuvant/adjuvant trials of pembrolizumab (KEYNOTE-522) and atezolizumab (NSABP B-59/GBG 96-GeparDouze) for localized triple-negative breast cancer (TNBC) (27:36) Ten-year update of the OlympiA trial of adjuvant olaparib for patients with germline BRCA1/2-mutated HER2-negative localized breast cancer (31:23) Exploratory analysis of patients who did or did not receive prior PD-1/PD-L1 inhibition in the Phase III OptiTROP-Breast01 study of sacituzumab tirumotecan versus chemotherapy for previously treated advanced TNBC (32:56) CNS efficacy of T-DXd (DESTINY-Breast12 trial) and outcomes with palbociclib combined with anti-HER2 therapy (AFT-38 PATINA trial) for HER2-positive mBC (34:04) CME information and select publications

In this episode, our guest is Lewis Bender, Chairman, and CEO, of Intensity Therapeutics' Founder which is a late-stage clinical biotechnology company whose mission is to help patients live longer, higher quality lives by discovering, developing, and commercializing first-in-class cancer drugs that attenuate tumors with minimal side effects, while training the patient's immune system to fight the cancer.  The Company's lead product candidate, INT230-6, is currently in human clinical studies to treat refractory solid tumors.Talking points:Milestone Achievement: "Congratulations on dosing the first patient in the INVINCIBLE-4 Phase 2 clinical trial for triple-negative breast cancer. Can you walk us through the significance of this milestone and what it means for the future of Intensity Therapeutics?"Innovative Approach of INT230-6: "Intensity Therapeutics focuses on developing cancer treatments that not only attenuate tumors with minimal side effects but also train the immune system to fight cancer. Could you explain how your lead product, INT230-6, achieves this unique approach and what differentiates it from existing cancer therapies?"Collaboration with SAKK: "Your partnership with The Swiss Group for Clinical Cancer Research (SAKK) is a key component of the INVINCIBLE-4 study. How does this collaboration enhance your clinical development efforts, and what are you hoping to achieve together in this trial?"Impact on Triple-Negative Breast Cancer (TNBC): "Triple-negative breast cancer is known for being particularly aggressive and having limited treatment options. How does INT230-6 address the unmet needs of TNBC patients, and what potential impact do you foresee it having on improving patient outcomes?"Future Vision and Next Steps: "Looking ahead, what are the next steps for Intensity Therapeutics following the initiation of the INVINCIBLE-4 study? How do you envision the future of your company in the evolving landscape of cancer therapeutics?"Guest - Lewis BenderHost - Hillary Blackburn, PharmD, MBAhttps://www.linkedin.com/in/hillary-blackburn-67a92421/ @talktoyourpharmacist for Instagram and Facebook ★ Support this podcast on Patreon ★

Since 2009, CancerCare and the Triple Negative Breast Cancer Foundation have partnered to provide vital support to those affected by TNBC. In this episode of Cancer Out Loud, host Cassie Spector (oncology social worker and CancerCare's Breast and Gynecological Cancer Program Coordinator) speaks with Allison McNeill, a Triple Negative Breast Cancer (TNBC) Day ambassador, about her experience with TNBC. They discuss the challenges of diagnosis, treatment, and survivorship and the importance of support systems and community. Allison shares her experiences navigating family dynamics, communicating with her children, and balancing work and health during treatment. The conversation emphasizes the need for advocacy, awareness, and the emotional complexities of living with TNBC . Episode Takeaways:- Trust what the doctors are saying.- Don't Google things; trust the process.- It's okay to let go of control a little bit.- Stay active, get outside, and connect with nature.- Don't react until there's something to react to.- You have to meet this new version of yourself.- Just say yes to help when it's offered.- Knowledge is power in this area.- It's okay to push back and ask questions.

In this special episode, I sit down with Ricki Fairley of TOUCH, The Black Breast Cancer Alliance and Hayley Dinerman of the Triple Negative Breast Cancer Foundation to discuss the latest advancements in TNBC research, including key takeaways from SABCS 2024, new immunotherapy and targeted therapies, and the impact of the AACR research grant. We also explore efforts to address racial disparities, upcoming awareness initiatives, and how you can get involved. Don't miss this insightful conversation about the future of TNBC treatment and advocacy. Thank you to Merck, Daiichi-Sankyo, Gilead, Pfizer, and Lilly for making this episode possible!  

It is Triple Negative Breast Cancer Day – an annual opportunity to bring more awareness to this aggressive type of breast cancer that is difficult to treat because it lacks an estrogen, progesterone and HER2 receptor. It primarily affects younger women and Black women and can spread quickly and be deadly if left untreated for too long. Treatment for TNBC used to include the toughest forms of chemotherapy, with debilitating side effects – but we've come a long way in how we treat patients with Triple Negative Breast Cancer so their outcomes are better. Today, we are speaking with Dr. Heather McArthur of UT Southwestern. She is a former Susan G. Komen grantee, Professor and the Komen Distinguished Chair in Clinical Breast Cancer Research. Dr. McArthur has been working on a Phase 3 clinical trial called KEYNOTE-522, which is testing whether a specific immunotherapy drug improves overall survival for people with high-risk early Triple Negative Breast Cancer. Dr. McArthur, along with her colleagues, are trying to determine if all people with this type of breast cancer truly need the drug, and if not, who would most benefit from taking it.

Welcome to the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain are joined by Dr. Virginia Kaklamani from the UTHealth San Antonio MD Anderson Cancer Center to discuss the latest advances in the treatment of triple negative breast cancer (TNBC) as we kick off 2025. •⁠  ⁠The treatment paradigms for early-stage TNBC, including the role Sacituzumab and radiation therapy. •⁠  ⁠Insights from the SABCS 2024 conference, focusing on the keynote 522 regimen and its implications for neoadjuvant treatment. •⁠  ⁠The management of locally advanced and metastatic TNBC, including the use of immunotherapy and the importance of PD-L1 testing. •⁠  ⁠Strategies for managing toxicities associated with treatments like sacituzumab and T-DXd. Whether you're a healthcare professional or someone interested in the latest in oncology, this episode provides valuable insights into the evolving landscape of breast cancer treatment. Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers! Key Takeaways: •⁠  ⁠Current standard of care for locally advanced TNBC. •⁠  ⁠The significance of chemotherapy and immunotherapy in treatment plans. •⁠  ⁠Managing toxicities in metastatic disease. Stay tuned for more discussions on treatment algorithms, FDA approvals, and clinical pearls in oncology! YouTube: https://youtu.be/GfROoYPVb_8 Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers

In this enlightening episode of the Patient From Hell, host Samira Daswani interviews Dr. Sara Tolaney, a leading oncologist specializing in breast cancer. They delve into the evolving landscape of triple-negative breast cancer (TNBC), exploring advancements in treatment, from targeted therapies to immunotherapy, and the challenges faced by patients in both early-stage and metastatic settings. With her characteristic warmth and expertise, Dr. Tolaney provides actionable insights for patients and caregivers, offering hope and understanding in navigating this complex diagnosis. Key Highlights: 1. A New Paradigm in Early-Stage TNBC Treatment: Dr. Tolaney explains how neoadjuvant chemotherapy combined with immunotherapy has revolutionized outcomes, achieving pathologic complete response rates above 60%. 2. Metastatic TNBC Advances: The discussion highlights the critical role of biomarker testing and the introduction of innovative therapies like antibody-drug conjugates, providing extended survival for many patients. 3. Empowering Patient Symptom Management: The episode underscores the importance of patient-reported outcomes and emerging tools like health apps to enhance self-management and real-time support for side effects. About our guest: Sara Tolaney, MD, MPH is the Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, and is internationally recognized for her research and education leadership in breast cancer. She also serves as Associate Director of the Susan F. Smith Center for Women's Cancers and is a Senior Physician at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School. Dr. Tolaney received her undergraduate degree from Princeton University and her medical degree from UC San Francisco. She subsequently completed her residency in Internal Medicine at Johns Hopkins University, and fellowships in hematology and medical oncology at Dana-Farber Cancer Institute. She obtained her Masters in Public Health from Harvard School of Public Health. Her research focuses on the development of novel therapies in the treatment of breast cancer and developing more effective and less toxic treatment approaches. Her work has demonstrated that a relatively low risk regimen is beneficial in women with early stage node-negative HER2-positive cancers, and this works has been incorporated into national and international guidelines. She has developed several follow-up studies looking at novel approaches to early stage HER2-positive disease and has also played a significant role in development of cdk 4/6 inhibitors, antibody drug conjugates, and immunotherapy in breast cancer. She is the author of over 150 peer-reviewed publications with manuscripts included in many prestigious journals such as the New England Journal, Lancet Oncology, Journal of Clinical Oncology, and JAMA Oncology. Key Moments: At 8 minutes: "It used to be that if someone had a triple negative breast cancer, we would often take someone to surgery and then after surgery give them some chemotherapy to kill any stray cells that might've gotten into the bloodstream and integrate radiation as needed. But we've really changed our approach very dramatically over the last few years where we've learned that if someone has an early stage, stage two or three triple negative breast cancer, it is actually very critical that they not go to upfront surgery, but in fact get chemotherapy with immunotherapy prior to surgery." Disclaimer: All content and information provided in connection with Manta Cares is solely intended for informational and educational purposes only. This content and information is not intended to be a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.

In this episode, I'm thrilled to welcome Dr. Tiffany Troso, a medical oncologist with over 25 years of experience in treating breast and gynecological cancers. We'll unpack some of the most important updates from this year's San Antonio Breast Cancer Symposium (SABCS) in a way that's clear and easy to follow. We'll cover topics like the latest on SERDS and how they're changing treatment options, the practice-changing findings from the PATINA trial, and exciting progress on a TNBC vaccine. Dr. Troso also sheds light on the growing movement toward treatment de-escalation and what it means for creating more personalized approaches to care. This episode is packed with valuable information to help patients and advocates feel informed and prepared to navigate their health journey. A special thank you to our “Your Guide to SABCS sponsors” Lilly, Gilead, Merck, Daiichi-Sankyo and Pfizer for making this episode possible.

Featuring perspectives from Dr Priyanka Sharma and Dr Sara M Tolaney, including the following topics: Introduction: Metastatic Triple-Negative Breast Cancer (mTNBC) — The Patient Perspective (0:00) Selection and Sequencing of Antibody-Drug Conjugates (5:09) Dosing and Tolerability of Sacituzumab Govitecan; Use of Anthracyclines (14:39) Case: A woman in her early 60s with relapsed TNBC (HER2 2+) who experiences disease progression on T-DXd (Grade 2 interstitial lung disease) and receives sacituzumab govitecan — Shaachi Gupta, MD, MPH (22:04) Discussing Palliative and End-of-Life Care (32:40) PARP Inhibitors for TNBC with Somatic versus Germline Mutations; Cytopenias with PARP Inhibitors (37:53) The “Art of Oncology” — Building Trust with Patients and Family Members (45:05) Case: A woman in her mid 60s with recurrent TNBC with extensive chest wall involvement — Dr Gupta (48:44) Case: A man in his mid 40s with multiregimen-refractory AR-positive TNBC with an ERBB2 exon 20 insertion mutation — Dr Gupta (52:53) CME information and select publications

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers. It affects younger women, women of African descent, and those with BRCA1 mutations. TNBC is highly complex, with distinct subtypes that may respond differently to treatments. Recent advancements include immunotherapies, androgen receptor inhibitors, platinum-based drugs, antibody-drug conjugates, PARP inhibitors, and combination therapies. These podcast episodes address educational gaps in TNBC management, offering interactive cases, discussions on emerging treatments, and strategies to improve patient outcomes.Launch Date: December 5, 2024Release Date: December 5, 2024Expiration Date: November 30, 2025FACULTYAditya Bardia, MD, MPH, FASCOAssociate Professor, Medicine, Harvard Medical SchoolAttending Physician, Medical Oncology, Massachusetts General HospitalDana-Farber/Harvard Cancer Center, Boston, MARita Nanda, MDAssociate Professor of MedicineDirector, Breast Oncology ProgramThe University of Chicago Medicine Chicago, ILThis podcast provides accredited continuing education credits.  To receive your credit, please read the accreditation information provided at this link below prior to listening to this podcast.https://www.practicepointcme.com/CMEHome/talking-tnbc-advancing-treatment-in-triple-negative-breast-cancer-latest-insights-and-clinical-strategies-19

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers. It affects younger women, women of African descent, and those with BRCA1 mutations. TNBC is highly complex, with distinct subtypes that may respond differently to treatments. Recent advancements include immunotherapies, androgen receptor inhibitors, platinum-based drugs, antibody-drug conjugates, PARP inhibitors, and combination therapies. These podcast episodes address educational gaps in TNBC management, offering interactive cases, discussions on emerging treatments, and strategies to improve patient outcomes.Launch Date: December 5, 2024Release Date: December 5, 2024Expiration Date: November 30, 2025FACULTYAditya Bardia, MD, MPH, FASCOAssociate Professor, Medicine, Harvard Medical SchoolAttending Physician, Medical Oncology, Massachusetts General HospitalDana-Farber/Harvard Cancer Center, Boston, MARita Nanda, MDAssociate Professor of MedicineDirector, Breast Oncology ProgramThe University of Chicago Medicine Chicago, ILThis podcast provides accredited continuing education credits.  To receive your credit, please read the accreditation information provided at this link below prior to listening to this podcast.https://www.practicepointcme.com/CMEHome/talking-tnbc-advancing-treatment-in-triple-negative-breast-cancer-latest-insights-and-clinical-strategies-19

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers. It affects younger women, women of African descent, and those with BRCA1 mutations. TNBC is highly complex, with distinct subtypes that may respond differently to treatments. Recent advancements include immunotherapies, androgen receptor inhibitors, platinum-based drugs, antibody-drug conjugates, PARP inhibitors, and combination therapies. These podcast episodes address educational gaps in TNBC management, offering interactive cases, discussions on emerging treatments, and strategies to improve patient outcomes.Launch Date: December 5, 2024Release Date: December 5, 2024Expiration Date: November 30, 2025FACULTYAditya Bardia, MD, MPH, FASCOAssociate Professor, Medicine, Harvard Medical SchoolAttending Physician, Medical Oncology, Massachusetts General HospitalDana-Farber/Harvard Cancer Center, Boston, MARita Nanda, MDAssociate Professor of MedicineDirector, Breast Oncology ProgramThe University of Chicago Medicine Chicago, ILThis podcast provides accredited continuing education credits.  To receive your credit, please read the accreditation information provided at this link below prior to listening to this podcast.https://www.practicepointcme.com/CMEHome/talking-tnbc-advancing-treatment-in-triple-negative-breast-cancer-latest-insights-and-clinical-strategies-19

Dr Priyanka Sharma from The University of Kansas Cancer Center in Westwood and Dr Sara M Tolaney from Dana-Farber Cancer Center in Boston discuss recent updates on available and novel treatment strategies for metastatic triple-negative breast cancer, moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/FCS2024mTNBC).

In this podcast, a study from Ontario revealed that SGLT2 inhibitors, when combined with statins, were associated with a 25% lower risk of rhabdomyolysis compared to DPP4 inhibitors. A phase I trial at Washington University demonstrated promising outcomes for a neoantigen DNA vaccine aimed at preventing recurrence in triple-negative breast cancer (TNBC). Finally, intensive systolic blood pressure control in Chinese patients with type 2 diabetes and elevated cardiovascular risk significantly reduced major cardiovascular events compared to standard care.

Featuring an interview with Dr Tiffany A Traina, including the following topics: Choice of chemotherapy to combine with first-line pembrolizumab for metastatic triple-negative breast cancer (mTNBC) (0:00) Ongoing investigations of androgen receptor-targeting agents for metastatic breast cancer (mBC) (8:37) Efficacy and CNS activity of sacituzumab govitecan for mTNBC; monitoring and management of treatment-associated side effects (14:34) Activity and tolerability of enfortumab vedotin for mTNBC (21:47) Rationale for combining antibody-drug conjugates with other systemic therapies for TNBC; early data and ongoing research efforts with combination approaches (24:13) Selection and sequencing of therapeutic options for advanced breast cancer (26:36) Clinical activity of trastuzumab deruxtecan; spectrum, severity and management of treatment-emergent toxicities (32:00) Case: A woman in her early 60s with mTNBC receives first-line pembrolizumab/carboplatin/gemcitabine (35:32) Case: A woman in her late 30s with TNBC and a short disease-free interval with adjuvant therapy is found to have CNS metastases that are treated with sacituzumab govitecan (40:40) Case: A woman in her late 60s and practicing physician is diagnosed with HR-negative, HER2-low mBC (44:16) CME information and select publications

Featuring a slide presentation and related discussion from Dr Tiffany A Traina, including the following topics: Extended follow-up with pembrolizumab/chemotherapy for patients with previously untreated PD-L1-positive metastatic triple-negative breast cancer (mTNBC) (0:00) ASCENT trial: Survival advantage with sacituzumab govitecan versus physician's choice of chemotherapy for patients with relapsed/refractory TNBC (2:49) Treatment-associated side effects with sacituzumab govitecan (5:32) Activity of sacituzumab govitecan irrespective of TROP2 expression level and in patients with brain metastases (6:48) Ongoing Phase III studies evaluating sacituzumab govitecan in earlier lines of treatment (eg, ASCENT-03, ASCENT-04) (8:51) Efficacy and tolerability of trastuzumab deruxtecan in patients with HER2-low and HER2-ultralow metastatic breast cancer (10:26) Activity and ongoing investigations of other novel agents and strategies for mTNBC (20:05) CME information and select publications

Dr Tiffany Traina from the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College in New York, New York, discusses optimizing the management of metastatic BRCA-negative, triple-negative breast cancer, moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/OncologyTodayBRCANegTNBC24).

8.14.2024 #RolandMartinUnfiltered: TNBC Endorses VP Harris,Evangelicals for Harris,Avoiding Election Misinformation,FAMU's Resignations The International Brotherhood of Teamsters has not officially endorsed Vice President Kamala Harris for President but she did receive one from the National Black Caucus of the International Brotherhood of Teamsters instead. The National Chairman of the TNBC will explain why they voted to support the Harris-Walz ticket.  "Evangelicals for Harris" is hosting a Zoom call tonight after dropping an ad showing Trump saying he doesn't ask God's forgiveness. In our Tech Talk segment, we'll talk to an expert about avoiding election misinformation on the internet.  FAMU's interim president is asking the university's senior leadership to resign.    And we remember the life of actor Erica Ash.  We'll show you some of her homegoing service.  Download the #BlackStarNetwork app on iOS, AppleTV, Android, Android TV, Roku, FireTV, SamsungTV and XBox  http://www.blackstarnetwork.com The #BlackStarNetwork is a news reporting platforms covered under Copyright Disclaimer Under Section 107 of the Copyright Act 1976, allowance is made for "fair use" for purposes such as criticism, comment, news reporting, teaching, scholarship, and research.See omnystudio.com/listener for privacy information.

How do you navigate breast cancer when you know the health care system is stacked against you? And, how, as a health care provider, can you best support marginalized people going through the experience of breast cancer? Let's find out. In this episode, Jasmine Samuel, a TNBC survivor and Black nurse shares how her experience of suboptimal care in Jackson, Miss., encouraged her to actively seek out a better care experience from MD Anderson in Houston, Texas. We'll also hear from Komen Scholar Dr. Mariana Chavez MacGregor, a breast medical oncologist and professor at the Breast Medical Oncology Department of MD Anderson Cancer Center who will discuss how she provides compassionate care and focuses research on improving outcomes for underserved patients.