Podcasts about serds

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  

After surgery, many people with stage I to stage III hormone receptor-positive breast cancer take tamoxifen or an aromatase inhibitor for five to 10 years. This has been the standard of care for the last 25 years. At the 2025 San Antonio Breast Cancer Symposium, UCLA scientist Dr. Aditya Bardia presented results on giredestrant, a new oral selective estrogen degrader/downregulator (SERD) that offered better disease-free survival — how long people live without the cancer returning – than tamoxifen or an aromatase inhibitor. Listen to the episode to hear Dr. Bardia explain: how giredestrant is different from the two other available SERDs if giredestrant could be combined with a CDK4/6 inhibitor giredestrant side effects what the results mean for people diagnosed with early-stage hormone receptor-positive breast cancer

Where do oral selective estrogen receptor degraders (SERDs) fit in the overall landscape of first- and second-line advanced/metastatic breast cancer? Credit available for this activity expires: 12/04/26 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/how-are-oral-serds-changing-management-advanced-hr-positive-2025a1000xkg?ecd=bdc_podcast_libsyn_mscpedu

Featuring perspectives from Dr Komal Jhaveri and Dr Virginia Kaklamani, including the following topics:  Introduction: Oral Selective Estrogen Receptor Degraders (SERDs) for the General Medical Oncologist (0:00) SERD Monotherapy (13:34) SERD and CDK Inhibitor Combination — The EMBER-3 Study (35:58) SERDs for "Molecular Progression" — The SERENA-6 Study (41:25) CME information and select publications

Featuring an interview with Dr Erika Hamilton, including the following topics: General overview of the mechanisms of action of endocrine-targeted therapies for breast cancer (0:00) Downregulation of estrogen receptor expression levels with endocrine therapy; therapeutic benefit of selective estrogen receptor degraders (SERDs) and proteolysis-targeting chimeras (PROTACs) in ESR1 wild-type and ESR1-mutant breast cancer (5:11) Mechanisms of resistance to endocrine therapy (10:08) Efficacy and toxicities observed with SERDs and PROTACs for HR-positive breast cancer (15:26) Other applications for PROTACs (24:24) Emerging data from the Phase III evERA trial (27:38) Perspectives on clinical investigator and general medical oncologist practice pattern survey results (30:51) CME information and select publications

Featuring slide presentations and related discussion from Prof Francois-Clement Bidard, Dr Hope S Rugo, Dr Rebecca Shatsky and Dr Seth Wander, including the following topics: Optimal approach to biomarker testing for patients with ER-positive metastatic breast cancer (mBC) (0:00) Case: A woman in her early 70s with recurrent ER-positive, HER2-negative mBC receives elacestrant (15:15) Case: A woman in her early 60s with ER-positive, HER2-low, PIK3CA-mutated mBC receives inavolisib-based therapy and experiences no disease progression for 24 months (18:02) Role of oral selective estrogen receptor degrader (SERD) monotherapy in the treatment of progressive ER-positive, HER2-negative mBC (26:26) Case: A woman in her mid 60s with recurrent HR-positive, HER2-negative mBC receives elacestrant (44:12) Case: A woman in her early 50s with recurrent HR-positive, HER2-negative, PIK3CA-mutant mBC receives capivasertib and fulvestrant (45:33) Potential novel applications of oral SERDs in the management of ER-positive, HER2-negative breast cancer (51:25) Case: A woman in her mid 50s with recurrent ER-positive, HER2-negative, PIK3CA-mutated mBC experiences disease progression 18 months after starting first-line letrozole and ribociclib (1:03:46) Case: A woman in her mid 50s with ER-positive, HER2-negative breast cancer undergoes serial ctDNA monitoring during first-line therapy (1:06:54) Tolerability and other practical considerations with oral SERDs (1:14:30) Case: A woman in her early 60s with recurrent HR-positive, HER2-negative mBC receives elacestrant (1:33:26) Case: A woman in her early 60s with recurrent HR-positive, HER2-negative mBC receives elacestrant (1:37:38) CME information and select publications

Prof Francois-Clement Bidard from the Institut Curie in Paris, France, Dr Hope S Rugo from the City of Hope Comprehensive Cancer Center in Duarte, California, Dr Rebecca Shatsky from the University of California San Diego Moores Cancer Center and Dr Seth Wander from Massachusetts General Hospital in Boston discuss recent updates on available and emerging treatment strategies involving oral SERDs for ER-positive metastatic breast cancer. CME information and select publications here.

Please visit answersincme.com/XCG860 to participate, download slides and supporting materials, complete the post test, and obtain credit. This educational activity brings together leading experts in ophthalmology and oncology to explore clinical strategies for managing ocular adverse events associated with a novel class of therapies for advanced breast cancer: the oral selective estrogen receptor degraders (SERDs). Faculty will share key insights and practical guidance on identifying and managing common ocular side effects—particularly photopsia and dry eye—with the goal of enhancing patient care and improving quality of life for individuals navigating survivorship with advanced breast cancer. Upon completion of this activity, participants should be better able to: Recognize the implications of using oral SERDs in HR-positive, HER2-negative breast cancer for ophthalmic practice; Describe the ocular toxicities associated with oral SERDs used in breast cancer treatment; and Apply multidisciplinary strategies to facilitate the detection and management of ocular toxicities in patients receiving oral SERDs.

Please visit answersincme.com/XCG860 to participate, download slides and supporting materials, complete the post test, and obtain credit. This educational activity brings together leading experts in ophthalmology and oncology to explore clinical strategies for managing ocular adverse events associated with a novel class of therapies for advanced breast cancer: the oral selective estrogen receptor degraders (SERDs). Faculty will share key insights and practical guidance on identifying and managing common ocular side effects—particularly photopsia and dry eye—with the goal of enhancing patient care and improving quality of life for individuals navigating survivorship with advanced breast cancer. Upon completion of this activity, participants should be better able to: Recognize the implications of using oral SERDs in HR-positive, HER2-negative breast cancer for ophthalmic practice; Describe the ocular toxicities associated with oral SERDs used in breast cancer treatment; and Apply multidisciplinary strategies to facilitate the detection and management of ocular toxicities in patients receiving oral SERDs.

Featuring an interview with Prof Patrick Neven, including the following topics: Emergence of ESR1 mutations in ER-positive, HER2-negative breast cancer (0:00) Observed toxicity profile of oral selective estrogen receptor degraders (SERDs) (3:57) Emerging data with novel oral SERD combinations (6:31) Challenges for a general medical oncologist in breast cancer (8:41) Sequencing and selection of therapies in ER-positive, HER2-negative breast cancer (12:16) Evaluating the strategy of switching to an oral SERD during first-line endocrine therapy upon "molecular progression" (23:16) CME information and select publications

Prof Patrick Neven from University Hospitals Leuven in Leuven, Belgium, discusses recent updates on available and novel treatment strategies with oral SERDs for ER-positive metastatic breast cancer. CME information and select publications here.

Featuring a slide presentation and related discussion from Prof Patrick Neven, including the following topics: Biology of the estrogen receptor (ER) and mechanisms of resistance to therapy (0:00) Clinical trial data involving oral selective ER degraders (SERDs) for endocrine-resistant ER-positive, HER2-negative metastatic breast cancer (13:34) Utility of switching to an oral SERD before radiographic disease progression for patients receiving first-line endocrine treatment (23:12) Ongoing trials with oral SERDs for ER-positive, HER2-negative breast cancer (27:13) Case: Patient with ER-positive, HER2-negative breast cancer receives imlunestrant upon disease progression on first-line letrozole (32:34) Case: Patient with ER-positive, HER2-negative breast cancer receives imlunestrant/abemaciclib upon relapse on letrozole/abemaciclib (34:16) Case: Patient with ER-positive, HER2-negative breast cancer receives camizestrant after first-line tamoxifen (36:20) Case: Patient with ER-positive, HER2-negative breast cancer receives elacestrant after disease progression on first-line letrozole/palbociclib (38:11) CME information and select publications

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/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AQV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 28, 2026.Visual Exploration of the Evolving Role of Novel Oral SERDs, Other ER-Targeting Therapies, and Rational Combinations in ER+, HER2- MBC In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. 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 activity is supported by an educational grant from Lilly.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/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XYR865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 24, 2026.Changing the Scenery in ER+, HER2- MBC With New Oral SERDs and Combinations: Foundations, Evidence, and Practicalities In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. 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 activity is supported by an educational grant from Lilly.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/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XYR865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 24, 2026.Changing the Scenery in ER+, HER2- MBC With New Oral SERDs and Combinations: Foundations, Evidence, and Practicalities In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. 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 activity is supported by an educational grant from Lilly.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/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AQV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 28, 2026.Visual Exploration of the Evolving Role of Novel Oral SERDs, Other ER-Targeting Therapies, and Rational Combinations in ER+, HER2- MBC In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. 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 activity is supported by an educational grant from Lilly.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/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XYR865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 24, 2026.Changing the Scenery in ER+, HER2- MBC With New Oral SERDs and Combinations: Foundations, Evidence, and Practicalities In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. 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 activity is supported by an educational grant from Lilly.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/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AQV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 28, 2026.Visual Exploration of the Evolving Role of Novel Oral SERDs, Other ER-Targeting Therapies, and Rational Combinations in ER+, HER2- MBC In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. 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 activity is supported by an educational grant from Lilly.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/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XYR865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 24, 2026.Changing the Scenery in ER+, HER2- MBC With New Oral SERDs and Combinations: Foundations, Evidence, and Practicalities In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. 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 activity is supported by an educational grant from Lilly.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/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AQV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 28, 2026.Visual Exploration of the Evolving Role of Novel Oral SERDs, Other ER-Targeting Therapies, and Rational Combinations in ER+, HER2- MBC In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. 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 activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, New York, and Dr Virginia Kaklamani from UT Health San Antonio MD Anderson Cancer Center in Texas review available efficacy and safety data guiding the optimal integration of oral SERDs into clinical practice. CME information and select publications here.

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  

Samira, a breast cancer survivor and CEO of Manta Cares, discusses the latest advancements in cancer treatment with Dr. Doug Blayney at the ASCO conference. They explore the significant impact of exercise on cancer treatment tolerance and survival, the de-escalation of chemotherapy, the introduction of new therapies like SERDs and antibody drug conjugates, and the role of circulating tumor DNA in monitoring cancer recurrence. The conversation emphasizes the importance of patient convenience and self-advocacy in cancer care.About Our Guest:Douglas W. Blayney, MD is a Professor of Medicine (Oncology), Emeritus, former Medical Director of Stanford Cancer Center, and specializes in the treatment of breast cancer. He has a special interest in the quality and value of cancer care. Dr. Blayney is a past president of the American Society of Clinical Oncology (ASCO), a founder of the ASCO Quality Symposium, a co-author of the ASCO value framework descriptions, and instigated the ASCO clinical "big data" effort, which is now CancerLinQ. He received the inaugural Ellen Stovall Award for Leadership in Patient Centered Care from the National Coalition for Cancer Survivorship in 2016. He was previously a Professor of Internal Medicine and Medical Director of the Comprehensive Cancer Center at the University of Michigan, and prior to that practiced and led Wilshire Oncology Medical Group, Inc. a physician owned multidisciplinary oncology practice in southern California. He has expertise on clinical trial development, use of oncology drugs in clinical practice, reimbursement and marketing strategies and information technology use.Chapter Codes00:00 The Impact of Exercise on Cancer Treatment02:00 Interview at ASCO Starts06:00 Advancements in Cancer Treatment: De-escalation and AI11:52 Emerging Therapies: SERDs and Antibody Drug Conjugates18:11 Circulating Tumor DNA: A New Frontier in Monitoring24:01 Convenience in Cancer Care: A Patient-Centric ApproachTakeaways- Regular exercise can increase tolerance to cancer treatments.- Data shows exercise has tangible benefits on survival rates.- De-escalation of chemotherapy is a key focus in cancer treatment.- AI is being integrated into cancer treatment guidelines.- Patients can take proactive steps to improve their health.- Oral SIRDs are emerging as a more convenient treatment option.- Antibody drug conjugates target cancer cells with fewer side effects.- Circulating tumor DNA can help detect cancer recurrence earlier.- Convenience in treatment is becoming a priority for patients.- Competition among treatments may help reduce costs for patients.Tags & Keywords:cancer treatment, ASCO, exercise, AI, SIRDs, antibody drug conjugates, circulating tumor DNA, patient care, chemotherapy, cancer survival, health technologyConnect with Us:Enjoyed this episode? Make sure to subscribe, rate, and review! Follow us on Instagram, Facebook, or Linkedin @mantacares and visit our website at mantacares.com for more episodes and updates.Listen Elsewhere: Website: https://mantacares.com/pages/podcast?srsltid=AfmBOopEP5GJ-Wd2nL-HYAInrwerIVhyJw67salKT-r9Qb_gadBvbHie YouTube: https://youtu.be/UjsAtpbedA8 Spotify: https://open.spotify.com/episode/7HwhjXHZU0ZWWVkXrCSV7V?si=d5e986f0885a4bbb Apple: https://podcasts.apple.com/us/podcast/cervical-cancer-and-hpv-what-you-need-to-know/id1622669098?i=1000710235401 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.

Dr Rinath Jeselsohn from the Dana-Farber Cancer Institute in Boston, Massachusetts, discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

Featuring an interview with Dr Rinath M Jesselsohn, including the following topics: Evaluating first-line treatment of metastatic ER-positive, HER2-positive breast cancer: heredERA Breast Cancer study (0:00) Kuemmel S et al. heredERA Breast Cancer: A phase III, randomized, open-label study evaluating the efficacy and safety of giredestrant plus the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with previously untreated HER2-positive, estrogen receptor-positive locally advanced or metastatic breast cancer. BMC Cancer 2024;24(1):641. Abstract  Treatment outcomes with CDK4/6 inhibitors and with elacestrant in real-world studies (4:13) Lloyd MR et al. CDK4/6 inhibitor efficacy in ESR1-mutant metastatic breast cancer. NEJM Evid 2024;3(5). Abstract  Lloyd M et al. Impact of prior treatment, ESR1 mutational (ESR1m) landscape, and co-occurring PI3K pathway status on real-world (RW) elacestrant outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC). San Antonio Breast Cancer Symposium 2024;Abstract PS7-05.  Evaluating the CNS activity of imlunestrant, an oral selective estrogen receptor degrader (SERD) (8:06) VandeKopple M et al. Preclinical characterization of imlunestrant, an oral brain-penetrant selective estrogen receptor degrader with activity in a brain metastasis (BM) model. ESMO Breast 2023;Abstract 41P.  Selective review of trials of oral SERDs in the adjuvant setting (11:27) A study of imlunestrant versus standard endocrine therapy in participants with early breast cancer (EMBER-4). NCT05514054 CME information and select publications

Featuring an interview with Dr Rinath M Jesselsohn, including the following topics: Imlunestrant with or without abemaciclib in advanced breast cancer: Results of the Phase III EMBER-3 trial (0:00) Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2025;392(12):1189-202. Abstract  Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the Phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1 and PTEN in HR-positive, HER2-negative metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice (7:00) Bhave MA et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: Prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res Treat 2024;207(3):599-609. Abstract Camizestrant, a next-generation oral selective estrogen receptor degrader (SERD), versus fulvestrant for postmenopausal women with estrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomized, Phase II trial (10:25) Oliveira M et al. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol 2024;25(11):1424-39. Abstract Latest on SERDs: An education session at San Antonio Breast Cancer Symposium 2024 (13:57) Jeselsohn RM. Latest on selective estrogen receptor degraders (SERDs). San Antonio Breast Cancer Symposium 2024;Education Session 5. CME information and select publications

Dr Rinath M Jeselsohn from the Dana-Farber Cancer Institute in Boston, Massachusetts, discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

This featured podcast includes a data review and candid conversation with 4 experts on challenges in the current treatment paradigm for hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (mBC) due to endocrine resistance. This session occurred during a satellite symposium held in conjunction with the 42nd Annual Miami Breast Cancer Conference® in March 2025.  ESR1 mutations are a critical mechanism of resistance, spurring the development of next-generation endocrine agents targeting these mutations. These agents including oral selective estrogen receptor degraders (SERDs) and agents with novel mechanisms, including proteolysis-targeting chimeras (PROTACs), which may offer potential improvements over current treatments. This program will review mechanisms of resistance to current endocrine regimens, strategies to overcome this resistance including comparative mechanisms of novel endocrine agents, emerging data from ongoing clinical trials, and expert perspectives on where these new agents may fit into current algorithms.

Featuring an interview with Dr Sara A Hurvitz, including the following topics: Role of endocrine therapy in the management of HER2-positive breast cancer; implications of the Phase III PATINA study (0:00) Case: A woman in her mid 60s with node-negative, HR-positive, HER2-negative localized breast cancer and a Recurrence Score® of 28 (8:38) Available data guiding the selection of an adjuvant CDK4/6 inhibitor (12:49) Selection of a CDK4/6 inhibitor in the metastatic setting (23:16) Available therapies for patients with HR-positive metastatic breast cancer (mBC) and PIK3CA mutations; implications of the Phase III INAVO120 study (29:17) Case: A woman in her early 60s with HR-positive, HER2-negative mBC with short duration of benefit from a first-line CDK4/6 inhibitor and an aromatase inhibitor (AI) and coexisting PIK3CA and ESR1 mutations (37:11) Available data with approved and investigational oral SERDs (selective estrogen receptor degraders) (43:23) Case: A woman in her early 70s with HR-positive, HER2-negative mBC and an ESR1 mutation detected on disease progression after durable responses to first-line endocrine therapy and second-line CDK4/6 inhibitor with an AI (51:38) Selection of therapy for patients with HR-positive mBC and coexisting targetable genetic mutations (53:11) Case: A woman in her late 50s with HR-positive, HER2-negative mBC and an ESR1 mutation detected on disease progression after first-line CDK4/6 inhibitor with an AI (1:00:17) CME information and select publications

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, New York, discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

Featuring an interview with Dr Komal Jhaveri, including the following topics: Emerging treatment options for advanced ER-positive breast cancer (0:00) Burstein H. Emerging treatment options for advanced ER+ breast cancer. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01 Discussant. Elacestrant real-world progression-free survival for adult patients with ER-positive, HER2-negative advanced breast cancer: A retrospective analysis using insurance claims in the United States (7:28) Swallow E et al. Elacestrant real-world progression-free survival (rwPFS) of adult patients with ER+/HER2-, advanced breast cancer: A retrospective analysis using insurance claims in the United States. San Antonio Breast Cancer Symposium 2024;Abstract P3-10-08. Ongoing clinical trials involving oral SERDs (9:03) Kaklamani V et al. ELCIN: Elacestrant in women and men with CDK4/6 inhibitor (CDK4/6i)-naïve estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC): An open-label multicenter phase 2 study. San Antonio Breast Cancer Symposium 2024;Abstract P2-08-20. An adjuvant endocrine-based therapy study of camizestrant (AZD9833) in ER+/HER2- early breast cancer (CAMBRIA-2). NCT05952557 Bardia A et al. ELEGANT: Elacestrant versus standard endocrine therapy in women & men with node-positive, estrogen receptor-positive, HER2-negative, early breast cancer with high risk of recurrence in a global, multicenter, randomized, open-label phase 3 study. San Antonio Breast Cancer Symposium 2024;Abstract P2-08-21. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer (13:48) Lloyd MR et al. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer. Nat Rev Clin Oncol 2024;21(10):743-61. Abstract CME information and select publications

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, New York, discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

Featuring an interview with Dr Komal Jhaveri, including the following topics: Imlunestrant, an oral selective estrogen receptor degrader (SERD), with and without abemaciclib for ER-positive, HER2-negative advanced or metastatic breast cancer (0:00) Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01. Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2024;[Online ahead of print]. Abstract Rugo HS et al. Elacestrant abemaciclib (abema) combination in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced or metastatic breast cancer (mBC). San Antonio Breast Cancer Symposium 2024; Abstract PS7-07. Elacestrant for ER-positive, HER2-negative metastatic breast cancer with ESR1-mutated tumors: Subgroup analyses from the Phase III EMERALD trial by duration of prior endocrine therapy with a CDK4/6 inhibitor and in clinical subgroups (7:40) Bardia A et al. Elacestrant in ER+, HER2- MBC with ESR1-mutated tumors: Subgroup analyses from the phase III EMERALD trial by prior duration of endocrine therapy plus CDK4/6 inhibitor and in clinical subgroups. Clin Cancer Res 2024;30(19):4299-309. Abstract Pharmacokinetics and safety of imlunestrant in patients with hepatic impairment (11:25) Wang XA et al. Evaluation of pharmacokinetics and safety of imlunestrant in participants with hepatic impairment. San Antonio Breast Cancer Symposium 2024;Abstract P4-10-07. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer (13:15) Lloyd MR et al. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer. Nat Rev Clin Oncol 2024;21(10):743-61. Abstract CME information and select publications

Dr Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here.

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here

Featuring an interview with Dr Seth Wander, including the following topics: Therapy selection after CDK4/6 inhibitor failure: A review of current and investigational treatment for HR-positive, HER2-negative breast cancer Astore S et al. A therapeutic algorithm guiding subsequent therapy selection after CDK4/6 inhibitors' failure: A review of current and investigational treatment for HR+/Her2- breast cancer. Crit Rev Oncol Hematol 2024;204:104535. Abstract (0:00) A preoperative window-of-opportunity study of the oral SERD imlunestrant for newly diagnosed ER-positive, HER2-negative localized breast cancer Neven P et al. A preoperative window-of-opportunity study of oral SERD, imlunestrant, in newly diagnosed ER-positive, HER2-negative early breast cancer: Results from the EMBER-2 Study. Clin Cancer Res 2024;30(23):5304-13. Abstract (3:30) An assessment of an exosome-based ESR1-monitoring RT-qPCR kit that detects acquired resistance variants in liquid biopsy samples Statt S et al. An exosome-based ESR1 monitoring RT-qPCR kit that rapidly and accurately detects acquired resistance variants at ≤ 0.1% frequency in liquid biopsy samples. ESMO 2024;Abstract 420P. (7:08) CME information and select publications

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here

Featuring an interview with Dr Seth Wander, including the following topics: The clinical utility of ESR1 mutations in HR-positive, HER2-negative advanced breast cancer Grinshpun A et al. The clinical utility of ESR1 mutations in hormone receptor-positive, HER2-negative advanced breast cancer. Hematol Oncol Clin North Am 2023;37(1):169-81. Abstract (0:00) Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and in combination with targeted therapy for ER-positive, HER2-negative advanced breast cancer Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and in combination with targeted therapy in estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Phase Ia/Ib EMBER study. J Clin Oncol 2024;[Online ahead of print]. Abstract (6:01) EORTC-2129-BCG: Elacestrant for ER-positive/HER2-negative breast cancer patients with ctDNA relapse Ignatiadis M et al. EORTC-2129-BCG: Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (TREAT ctDNA). ESMO 2024;Abstract 338TiP. (8:20) CME information and select publications  

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer. CME information and select publications here

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.

In this episode, listen to Virginia Kaklamani, MD, DSc; Erica L. Mayer, MD, MPH; and Laura M. Spring, MD, share their clinical insights and takeaways from a live symposium, including from key abstracts presented at the 2024 San Antonio Breast Cancer Symposium:Estrogen Receptor Mutations in Patients With HR-Positive/HER2-Negative Advanced Breast CancerCurrent Guideline Recommendations for When to Pursue ESR1 Mutation Testing Mutations in Patients With HR-Positive/HER2-Negative Advanced Breast CancerChoice and Sequencing of Next Line of Systemic Therapy for ESR1-Mutated Advanced Breast Cancer Based on Tumor Molecular AlterationsOverview of Class-Related and Unique Adverse Events With Approved and Emerging Oral SERDSExpert Recommendations for the Management of Oral SERDs-Related Adverse EventsProgram faculty:Virginia Kaklamani, MD, DScProfessor of MedicineRuth McLean Bowman Bowers Chair in Breast Cancer Research and TreatmentA.B. Alexander Distinguished Chair in Oncology LeaderBreast Oncology ProgramUT Health San AntonioMD Anderson Cancer CenterSan Antonio, TexasErica L. Mayer, MD, MPHDirector of Breast Cancer Clinical ResearchDana-Farber Cancer InstituteAssociate Professor in MedicineHarvard Medical SchoolBoston, MassachusettsLaura M. Spring, MDBreast Medical OncologistMass General Hospital Cancer CenterHarvard Medical SchoolBoston, Massachusetts Resources:To download the slides associated with this podcast discussion, please visit the program page.

Send us a textIn this episode, we are thrilled to welcome back Tiffany Troso-Sandoval MD, a distinguished medical oncologist with a quarter-century of experience in women's cancers. Dr. Troso shares her insights from a recent breast cancer symposium, illuminating groundbreaking patient care and treatment strategy advancements. As she shares her journey from the clinic to her broader role in cancer advocacy through her company, Winning The Cancer Journey, Dr. Troso unveils some of her plans aimed at educating and empowering both patients and caregivers.We explore the complex world of metastatic breast cancer treatment, emphasizing estrogen receptor-positive cases. We review the different types of anti-estrogen therapies including how and why they work.  We discuss the role of CDK4/6 inhibitors used with aromatase inhibitors, breaking down how these treatments target estrogen pathways to curb cancer growth. We navigate the intricacies of ESR1 mutations and explore how selective estrogen receptor degraders (SERDs) are crucial in overcoming treatment resistance. From chemotherapy timing to empowering caregivers, we delve into the multifaceted nature of breast cancer treatment decisions. Dr. Troso shares her transition from hands-on patient care to creating impactful online resources, highlighting the ongoing nature of the cancer journey for both patients and caregivers.  drtiffanytroso@winningthecancerjourney.comDr. Troso on Facebook Winning The Cancer Journey on FacebookDr. Troso on Instagram Winning The Cancer Journey on TikTok San Antonio Breast Cancer Symposium GuideCNN interview:  https://www.youtube.com/watch?v=MU38D89YlQ0 Are you loving the Test Those Breasts! Podcast? You can show your support by donating to the Test Those Breasts Nonprofit @ https://testthosebreasts.org/donate/ Where to find Jamie:Instagram LinkedIn TikTok Test Those Breasts Facebook Group LinkTree Jamie Vaughn in the News! Thanks for listening! I would appreciate your rating and review where you listen to podcasts!I am not a doctor and not all information in this podcast comes from qualified healthcare providers, therefore may not constitute medical advice. For personalized medical advice, you should reach out to one of the qualified healthcare providers interviewed on this podcast and/or seek medical advice from your own providers .

Featuring an interview with Dr Seth Wander, including the following topics: Design of SERENA-6, a Phase III switching trial of camizestrant for ESR1-mutant breast cancer during first-line treatment Turner N et al. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol 2023;19(8):559-73. Abstract (0:00) EMERALD trial analysis of patient-reported outcomes with oral elacestrant compared to standard of care endocrine therapy for ER-positive, HER2-negative advanced or metastatic breast cancer Cortes J et al. EMERALD trial analysis of patient-reported outcomes (PROs) in patients with ER+/HER2− advanced or metastatic breast cancer (mBC) comparing oral elacestrant vs standard of care (SoC) endocrine therapy. ESMO Breast 2023;Abstract 188O. (5:50) Imlunestrant, an oral selective estrogen receptor degrader, in combination with HER2-directed therapy, with or without abemaciclib, for ER-positive, HER2-positive advanced breast cancer Bhave MA et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), in combination with human epidermal growth factor receptor 2 (HER2) directed therapy, with or without abemaciclib, in estrogen receptor (ER) positive, HER2 positive advanced breast cancer (aBC): EMBER phase 1a/1b study. ASCO 2024;Abstract 1027. (9:43) CME information and select publications

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer.

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral SERDs in the management of ER-positive metastatic breast cancer, moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/5MJC2024/OralSERDsmBC/2).

Featuring an interview with Dr Seth Wander, including the following topics: ASCO Guidelines Rapid Recommendations Update for Testing for ESR1 Mutations (0:00) Real-world elacestrant use patterns and genomic biomarkers (4:43) Circulating tumor DNA (ctDNA) analyses with imlunestrant in the EMBER Phase I study (8:50) CME information and select publications

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral selective estrogen receptor degraders for ER-positive metastatic breast cancer.

Dr Seth Wander from Massachusetts General Hospital in Boston discusses recent developments with oral selective estrogen receptor degraders for ER-positive metastatic breast cancer, moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/5MJC2024/OralSERDsmBC/1).