Podcasts about cdk4

JCO Precision Oncology Conversations

Play Episode Listen Later Feb 19, 2026 21:50

In this episode of the Oncology Brothers podcast we navigated the rapidly evolving treatment landscape of Metastatic Hormone Receptor-Positive Breast Cancer. We were joined by Dr. Kevin Kalinsky, Director of the Breast Cancer Program at the Winship Cancer Institute, Emory University, to discuss the implications of new targeted therapies, optimal sequencing strategies, and practical toxicity management. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: •⁠ YouTube: https://www.youtube.com/@oncologybrothers •⁠ ⁠X/Twitter: https://twitter.com/oncbrothers •⁠ ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ The discussion covered: • The critical role of NGS testing (tissue vs. liquid biopsy) in identifying PIK3CA, ESR1, AKT1 and PTEN alterations. • Frontline management of high-risk, endocrine-resistant disease with the inavolisib triplet (INAVO120) and its overall survival benefit. • Choosing between CDK4/6 inhibitors (abemaciclib vs. ribociclib) in de novo metastatic disease. • Post-CDK4/6 inhibitors on progression we covered, the use of oral SERDs (imlunestrant) and AKT inhibitors (capivasertib). • The "ADC explosion", sequencing T-DXd (DESTINY-Breast06), sacituzumab govitecan (TROPiCS-02), and datopotamab deruxtecan (TROPION-Breast01). • Clinical pearls for managing toxicities: stomatitis, hyperglycemia, rash, neutropenia, and ILD. Join us as we break down the latest data and provide actionable insights for the practicing oncologist. Don't forget to subscribe for more episodes in our breast cancer algorithm series! #MetastaticBreastCancer, #HRPositive, #ADCsequencing, #PIK3CA-AKT, #OncologyPodcast, #OncologyBrothers

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ctDNA in Metastatic Invasive Lobular Carcinoma

Play Episode Listen Later Feb 18, 2026 27:46

JCO PO author Dr. Foldi at UPMC Hillman Cancer Center and University of Pittsburgh School of Medicine shares insights into the JCO PO article, "Personalized Circulating Tumor DNA Testing for Detection of Progression and Treatment Response Monitoring in Patients With Metastatic Invasive Lobular Carcinoma of the Breast." Host Dr. Rafeh Naqash and Dr. Foldi discuss how serial ctDNA testing in patients with mILC is feasible and may enable personalized surveillance and real-time therapeutic monitoring. TRANSCRIPT Dr. Rafeh Naqash: Hello, and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I am your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Associate Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today, we are thrilled to be joined by Dr. Julia Foldi, Assistant Professor of Medicine in the Division of Hematology-Oncology at University of Pittsburgh School of Medicine and the Magee-Womens Hospital of the UPMC. She is also the lead and corresponding author of the JCO Precision Oncology article entitled "Personalized Circulating Tumor DNA Testing for Detection of Progression and Treatment Response Monitoring in Patients with Metastatic Invasive Lobular Carcinoma of the Breast." At the time of this recording, our guest's disclosures will be linked in the transcript. Julia, welcome to our podcast, and thank you for joining us today. Dr. Julia Foldi: Thank you so much for having me. It is a pleasure. Dr. Rafeh Naqash: Again, your manuscript and project address a few interesting things, so we will start with the basics, since we have a broad audience that comprises trainees, community oncologists, and obviously precision medicine experts as well. So, let us start with invasive lobular breast carcinoma. I have been out of fellowship for several years now, and I do not know much about invasive lobular carcinoma. Could you tell us what it is, what some of the genomic characteristics are, why it is different, and why it is important to have a different way to understand disease biology and track disease status with this type of breast cancer? Dr. Julia Foldi: Yes, thank you for that question. It is really important to frame this study. So, lobular breast cancers, which we shorten to ILC, are the second most common histologic subtype of breast cancer after ductal breast cancers. ILC makes up about 10 to 15 percent of all breast cancers, so it is relatively rare, but in the big scheme of things, because breast cancer is so common, this represents actually over 40,000 new diagnoses a year in the US of lobular breast cancers. What is unique about ILC is it is characterized by loss of an adhesion molecule, E-cadherin. It is encoded by the CDH1 gene. What it does is these tumors tend to form discohesive, single-file patterns and infiltrate into the tumor stroma, as opposed to ductal cancers, which generally form more cohesive masses. As we generally explain to patients, ductal cancers tend to form lumps, while lobular cancers often are not palpable because they infiltrate into the stroma. This creates several challenges, particularly when it comes to imaging. In the diagnostic setting, we know that mammograms and ultrasounds have less sensitivity to detect lobular versus ductal breast cancer. When it comes to the metastatic setting, conventional imaging techniques like CT scans have less sensitivity to detect lobular lesions often. One other unique characteristic of ILC is that these tumors tend to have lower proliferation rates. Because our glucose-based PET scans depend on glucose uptake of proliferating cells, often these tumors also are not avid on conventional FDG-PET scans. It is a challenge for us to monitor these patients as they go through treatment. If you think about the metastatic setting, we start a new treatment, we image people every three to four cycles, about every three months, and we combine the imaging results with clinical assessment and tumor markers to decide if the treatment is working. But if your imaging is not reliable, sometimes even at diagnosis, to really detect these tumors, then really, how are we following these patients? This is really the unique challenge in the metastatic setting in patients with lobular breast cancer: we cannot rely on the imaging to tell if patients are responding to treatment. This is where liquid biopsies are really, really important, and as the field is growing up and we have better and better technologies, lobular breast cancer is going to be a field where they are going to play an important role. Dr. Rafeh Naqash: Thank you for that easy-to-understand background. The second aspect that I would like to have some context on, to help the audience understand why you did what you did, is ctDNA, tumor informed and non-informed. Could you tell us what these subtypes of liquid biopsies are and why you chose a tumor informed assay for your study? Dr. Julia Foldi: Yes, it is really important to understand these differences. As you mentioned, there are two main platforms for liquid biopsy assays, circulating tumor DNA assays. I think what is more commonly used in the metastatic setting are non-tumor informed assays, or agnostic assays. These are generally next-generation sequencing-based assays that a lot of companies offer, like Guardant, Tempus, Caris, and FoundationOne. These do not require tumor tissue; they just require a blood sample, a plasma sample, essentially. The next-generation sequencing is done on cell-free DNA that is extracted from the plasma, and it is looking for any cell-free DNA and essentially, figuring out what part of the cell-free DNA comes from the tumor is done through a bioinformatics approach. Most of these assays are panel tests for cancer-associated mutations that we know either have therapeutic significance or biologic significance. So, the results we receive from these tests generally read out specific mutations in oncogenic genes, or sometimes things like fusions where we have specific targeted drugs. Some of the newer assays can also read out tumor fraction; for example, the newest generation Guardant assay that is methylation-based, they can also quantify tumor fraction. But the disadvantage of the tumor agnostic approach is that it is a little bit less sensitive. Opposed to that, we have our tumor informed tests, and these require tumor tissue. Essentially, the tumor is sequenced; this can either be whole exome or whole genome sequencing. The newer generation assays are now using whole genome sequencing of the tumor tissue, and a personalized, patient-specific panel of alterations is essentially barcoded on that tumor tissue. This can be either structural variants or it can be mutations, but generally, these are not driver mutations, but sort of things that are present in the tumor tissue that tend to stay unchanged over time. For each particular patient, a personalized assay, if you want to call it a fingerprint or barcode, is created, and then that is what then is used to test the plasma sample. Essentially, you are looking for that specific cancer in the blood, that barcode or fingerprint in the blood. Because of this, this is a much more sensitive way of looking for ctDNA, and obviously, this detects only that particular tumor that was sequenced originally. So, it is much more sensitive and specific to that tumor that was sequenced. You can argue for both approaches in different settings. We use them in different settings because they give us different information. The tumor agnostic approach gives us mutations, which can be used to determine what the next best therapy to use is, while the tumor informed assay is more sensitive, but it is not going to give us information on therapeutic targets. However, it is quantified, and we can follow it over time to see how it changes. We think that it is going to tell us how patients respond to treatment because we see our circulating tumor DNA levels rise and fall as the cancer burden increases or decreases. We decided to use the tumor informed approach in this particular study because we were really interested in how to determine if patients are having response to treatment versus if they are going to progress on their treatment, more so than looking for specific mutations. Dr. Rafeh Naqash: When you think about these tumor informed assays and you think about barcoding the mutations on the original tumor that you try to track or follow in subsequent blood samples, plasma samples, in your experience, if you have done it in non-lobular cancers, do you think shedding from the tumor has something to do with what you capture or how much you capture? Dr. Julia Foldi: Absolutely. I think there are multiple factors that go into whether someone has detectable ctDNA or not, and that has to do with the type of cancer, the location, right, where is the metastatic site? This is something that we do not fully understand yet: what are tumors that shed more versus not? There is also clearance of ctDNA, and so how fast that clearance occurs is also something that will affect what you can detect in the blood. ctDNA is very short-lived, only has a half-life of hours, and so you can imagine that if there is little shedding and a lot of excretion, then you are not going to be detecting a lot of it. In general, in the metastatic setting, we see that we can detect ctDNA in a lot of cases, especially when patients are progressing on treatment, because we imagine their tumor burden is higher at that point. Even with the non-tumor informed assays, we detect a lot of ctDNA. Part of this study was to actually assess: what is the proportion of patients where we can have this information? Because if we are only going to be able to detect ctDNA in less than 50 percent of patients, then it is not going to be a useful method to follow them with. Because this field is new and we have not been using a lot of tumor informed assays in the metastatic setting, we did not really know what to expect when we set out to look at this. We did not know what was going to be the baseline detection rate in this patient population, so that was one of the first things that we wanted to answer. Dr. Rafeh Naqash: Excellent. Now going to this manuscript in particular, what was the research question, what was the patient population, and what was the strategy that you used to investigate some of these questions? Dr. Julia Foldi: So, we partnered with Natera, and the reason was that their Signatera tumor-informed assay was the first personalized, tumor-informed, really an MRD assay, minimal residual disease detection assay. It has been around the longest and has been pretty widely used commercially already, even though some of our data is still lacking. but we know that people are using this in the real world. We wanted to gather some real-world data specifically in lobular patients. So, we asked Natera to look at their database of commercial Signatera testing and look for patients with stage 4 lobular breast cancer. The information all comes from the submitting physicians sending in pathologic reports and clinical notes, and so they have that information from the requisitions essentially that are sent in by the ordering physician. We found 66 patients who were on first-line or close to first-line endocrine-based therapies for their metastatic lobular breast cancer and had serial collections of Signatera tests. The way we defined baseline was that the first Signatera had to be sent within three months of starting treatment. So, it is not truly baseline, but again, this is a limitation of looking at real-world data is that you are not always going to get the best time point that you need. We had over 350 samples from those 66 patients, again longitudinal ctDNA samples, and our first question was what is the baseline detection rate using this tumor informed assay? Then, most importantly, what is the concordance between changes in ctDNA and clinical response to treatment? That is defined by essentially radiologic response to treatment. Dr. Rafeh Naqash: Interesting. So, what were some of your observations in terms of ctDNA dynamics, whether baseline levels made a difference, whether subsequent levels at different time points made a difference, or subsequent levels at, let us say, cycle three made a difference? Were there any specific trends that you saw? Dr. Julia Foldi: So, first, at baseline, 95 percent of patients had detectable ctDNA, which is, I think, a really important data point because it tells us that this can be a really useful test. If we can detect it in almost all patients before they start treatment, we are going to be able to follow this longitudinally. And again, these were not true baseline samples. So, I think if we look really at baseline before starting treatment, almost all patients will have detectable ctDNA in the metastatic setting. The second important thing we saw was that disease progression correlated very well with increase in ctDNA. So, in most patients who had disease progression by imaging, we saw increase in ctDNA. Conversely, in most patients who had clinical benefit from their treatment, so they had a response or stable disease, we saw decrease in ctDNA levels. It seems that what we call molecular response based on ctDNA is tracking very nicely along with the radiographic response. So, those were really the two main observations. Again, this is a small cohort, limited by its real-world nature and the time points that ctDNA assay was sent was obviously not mandated. This is a real-world data set, and so we could not really look at specific time points like you asked about, let us say, cycle three of therapy, right? We did not have all of the right time points for all of the patients. But what we were able to do was to graph out some specific patient scenarios to illustrate how changes in ctDNA correlate with imaging response. I can talk a little bit about that. Dr. Rafeh Naqash: That was going to be my question. Did you see patients who had serial monitoring using the tumor informed ctDNA assay where the assay became positive a few months before the imaging? Did you have any of those kinds of observations? Dr. Julia Foldi: Yes, so I think this is where the field is going: are we able to use this technology to maybe detect progression before it becomes clinically apparent? Of course, there are lots of questions about: does that really matter? But it seems like, based on some of the patient scenarios that we present in the paper, that this testing can do that. So, we had a specific scenario, and this is illustrated in a figure in the paper, really showing the treatment as well as the changes in ctDNA, tumor markers, and also radiographic response. So, this particular patient was on first-line endocrine therapy and CDK4/6 inhibitor with palbociclib. Initially, she had a low-level detectable ctDNA. It became undetectable during treatment, and the patient had a couple of serial ctDNA assays that were negative, so undetectable. And then we started, after about seven months on this combination therapy, the ctDNA levels started rising. She actually had three serial ctDNA assays with increasing level of ctDNA before she even had any imaging tests. And then around the time that the ctDNA peaked, this patient had radiographic evidence of progression. There was also an NGS-based assay sent to look for specific mutations at that point. The patient was found to have an ESR1 mutation, which is very common in this patient population. She was switched to a novel oral SERD, elacestrant, and the ctDNA fell again to undetectable within the first couple months of being on elacestrant. And then a very similar thing happened: while she was on this second-line therapy, she had three serial negative ctDNA assays, and then the fourth one was positive. This was two months before the patient had a scan that showed progression again. Dr. Rafeh Naqash: And Julia, like you mentioned, this is a small sample size, limited number of patients, in this case, one patient case scenario, but provides insights into other important aspects around escalation or de-escalation of therapy where perhaps ctDNA could be used as an integral biomarker rather than an exploratory biomarker. What are some of your thoughts around that and how is the breast cancer space? I know like in GI and bladder cancer, there has been a significant uptrend in MRD assessments for therapeutic decision making. What is happening in the breast cancer space? Dr. Julia Foldi: So, super interesting. I think this is where a lot of our different fields are going. In the breast cancer space, so far, I have seen a lot of escalation attempts. It is not even necessarily in this particular setting where we are looking at dynamics of ctDNA, but in the breast cancer world, of course, we have a lot of data on resistance mutations. I mentioned ESR1 mutation in a particular patient in our study. ESR1 mutations are very common in patients with ER-positive breast cancer who are on long-term endocrine therapy, and ESR1 mutations confer resistance to aromatase inhibitors. So, that is an area that there has been a lot of interest in trying to detect ESR1 mutations earlier and switching therapy early. So, this was the basis of the SERENA-6 trial, which was presented last year at ASCO and created a lot of excitement. This was a trial where patients had non-tumor-informed NGS-based Guardant assay sent every three to six months while they were on first-line endocrine therapy with a CDK4/6 inhibitor. If they had an ESR1 mutation detected, they were randomized to either continue the same endocrine therapy or switch to an oral SERD. The trial showed that the population of patients who switched to the oral SERD did better in terms of progression-free survival than those who stayed on their original endocrine therapy. There are a lot of questions about how to use this in routine practice. Of course, it is not trivial to be sending a ctDNA assay every three to six months. The rate of detection of these mutations was relatively low in that study; again, the incidence increases in later lines of therapy. So, there are a lot of questions about whether we should be doing this in all of our first-line patients. The other question is, even the patients who stayed on their original endocrine therapy were able to stay on that for another nine months. So, there is this question of: are we switching patients too early to a new line of therapy by having this escalation approach? So, there are a lot of questions about this. As far as I know, at least in our practice, we are not using this approach just yet to escalate therapy. Time will tell how this all pans out. But I think what is even more interesting is the de-escalation question, and I think that is where tumor informed assays like Signatera and the data that our study generated can be applied. Actually, our plan is to generate some prospective data in the lobular breast cancer population, and I have an ongoing study to do that, to really be able to tease out the early ctDNA dynamics as patients first start on endocrine therapy. So, this is patients who are newly diagnosed, they are just starting on their first-line endocrine therapy, and measure, with sensitive assays, measure ctDNA dynamics in the first few months of therapy. In those patients who have a really robust response, that is where I think we can really think about de-escalation. In the patients whose ctDNA goes to undetectable after just a few weeks of therapy with just an endocrine agent, they might not even need a CDK4/6 inhibitor in their first-line treatment. So, that is an area where we are very interested in our group, and I know that other groups are looking at this too, to try to de-escalate therapy in patients who clear their ctDNA early on. Dr. Rafeh Naqash: Thank you so much. Well, lots of questions, but at the same time, progress comes through questions asked, and your project is one of those which is asking an interesting question in a rarer cancer and perhaps will lead to subsequent improvement in how we monitor these individuals and how we escalate or de-escalate therapy. Hopefully, we will get to see more of what you are working on in subsequent submissions to JCO Precision Oncology and perhaps talk more about it in a couple of years and see how the space and field is moving. Thanks again for sharing your insights. I do want to take one to two quick minutes talking about you as an investigator, Julia. If you could speak to your career pathway, your journey, the pathway to mentorship, the pathway to being a mentor, and how things have shaped for you in your personal professional growth. Dr. Julia Foldi: Sure, yeah, that is great. Thank you. So, I had a little bit of an unconventional path to clinical medicine. I actually thought I was going to be a basic scientist when I first started out. I got a PhD in Immunology right out of college and was studying not even anything cancer-related. I was studying macrophage signaling in inflammatory diseases, but I was in New York City. This was right around the time that the first checkpoint inhibitors were approved. Actually, some of my friends from my PhD program worked in Jim Allison's lab, who was the basic scientist responsible for ipilimumab. So, I got to kind of first-hand experience the excitement around bringing something from the lab into the clinic that actually changed really the course of oncology. And so, I got very excited about oncology and clinical medicine. So, I decided to kind of switch gears from there and I went back to medical school after finishing my PhD and got my MD at NYU. I knew I wanted to do oncology, so I did a research track residency and fellowship combined at Yale. I started working early on with the breast cancer team there. At the time, Lajos Pusztai was the head of translational research there at Yale, and I started working with him early in my residency and then through my fellowship. I worked on several trials with him, including a neoadjuvant checkpoint inhibitor trial in triple-negative breast cancer patients. During my last year in fellowship, I received a Conquer Cancer Young Investigator Award to study estrogen receptor heterogeneity using spatial transcriptomics in this subset of breast cancers that have intermediate estrogen receptor expression. From there, I joined the faculty at the University of Pittsburgh in 2022. So, I have been there about almost four years at this point. My interests really shifted slowly from triple-negative breast cancers towards ER-positive breast cancers. When I arrived in Pittsburgh, I started working very closely with some basic and translational researchers here who are very interested in estrogen signaling and mechanisms of resistance to endocrine therapy, and there is a large group here interested in lobular breast cancers. During my training, I was not super aware even that lobular breast cancer was a unique subtype of breast cancers, and that is, I think, changing a little bit. There is a lot more awareness in the breast cancer clinical and research community about ILC being a unique subtype, but it is not even really part of our training in fellowship, which we are trying to change. But I have become a lot more aware of this because of the research team here and through that, I have become really interested also on the clinical side. And so, we do have a Lobular Breast Cancer Research Center of Excellence here at the University of Pittsburgh and UPMC, and I am the leader on the clinical side. We have a really great team of basic and translational researchers looking at different aspects of lobular breast cancers, and some of the work that I am doing is related to this particular manuscript we discussed and the next steps, as I mentioned, a prospective study of early ctDNA dynamics in lobular patients. I also did some more clinical research work in collaboration with the NSABP looking at long-term outcomes of patients with lobular versus ductal breast cancers in some of their older trials. And so, that is, in a nutshell, a little bit about how I got here and how I became interested in ILC. Dr. Rafeh Naqash: Well, thank you for sharing those personal insights and personal journey. I am sure it will inspire other trainees, fellows, and perhaps junior faculty in trying to find their niche. The path, as you mentioned, is not always straight; it often tends to be convoluted. And then finding an area that you are interested in, taking things forward, and being persistent is often what matters. Dr. Julia Foldi: Thank you so much for having me. It was great. Dr. Rafeh Naqash: It was great chatting with you. And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. 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.

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Early Stage Hormone Receptor Positive (HR+) Breast Cancer Treatment Algorithm: Dr. Erica Mayer

Play Episode Listen Later Feb 12, 2026 26:51

In this episode of the Oncology Brothers podcast, hosts Rahul and Rohit Gosain dived deep into the evolving landscape of breast cancer treatment algorithms, focusing on early and locally advanced hormone receptor-positive breast cancer. Joined by Dr. Erica Mayer, a breast medical oncologist at the Dana-Farber Cancer Institute. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: •⁠ YouTube: https://www.youtube.com/@oncologybrothers/ •⁠ ⁠X/Twitter: https://twitter.com/oncbrothers •⁠ ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ The discussion covered: • The role of chemotherapy in early-stage hormone receptor-positive breast cancer, including the use of anthracyclines versus taxane-based approaches. • Insights from the TAILORx trial and the implications of Oncotype DX scores in treatment decisions. • The ongoing OFSET trial and its potential impact on premenopausal patients with low recurrence scores. • The use of CDK4/6 inhibitors, including ribociclib and abemaciclib, in the adjuvant setting, along with their side effect profiles and dosing considerations. • The significance of the recent lidERA trial results featuring giredestrant and its implications for future treatment strategies. Join us as we explore the latest data, treatment paradigms, and the importance of patient-shared decision-making in breast cancer care. Don't forget to subscribe for more insights and staying up to date in the field of cancer. #EarlyBreastCancer, #OncotypeDX, #CDK46inhibitors, #OralSERD, #AdjuvantTherapy, #OncologyBrothers

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S16 Ep1: Targeted Therapies Take Center Stage for Estrogen Receptor–Positive Breast Cancer: With Aditya Bardia, MD, MPH, FASCO

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Feb 10, 2026 9:15

In today's episode, our discussion features Aditya Bardia, MD, MPH, FASCO. Dr Bardia is a professor in the Department of Medicine in the Division of Hematology/Oncology, the director of Translational Research Integration, and a member of Signal Transduction and Therapeutics at the UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, California.In our exclusive interview, Dr Bardia discussed key findings from the phase 3 lidERA Breast Cancer study (NCT04961996) showing the invasive disease–free survival superiority of giredestrant (GDC-9545) over standard endocrine therapy in patients with estrogen receptor–positive, HER2-negative early breast cancer. Our discussion also covered the ongoing phase 3 INAVO123 trial (NCT06790693), which is investigating inavolisib (Itovebi) plus CDK4/6 inhibitors and letrozole in patients with endocrine-sensitive, PIK3CA-mutated breast cancer. Dr Bardia also emphasized the importance of testing for ESR1 and PIK3CA mutations in order to better personalize treatment.

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Sara A. Hurvitz, MD, FACP - Key Steps to Success With CDK4/6 Inhibition in Early Through Metastatic Breast Cancer: Stratification, Selection, Sequencing, and Specialty Management

Play Episode Listen Later Feb 4, 2026 83:40

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/CTJ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 6, 2027.Key Steps to Success With CDK4/6 Inhibition in Early Through Metastatic Breast Cancer: Stratification, Selection, Sequencing, and Specialty Management In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and Living Beyond Breast Cancer. 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 educational grants from Lilly and Novartis Pharmaceuticals Corporation.Disclosure information is available at the beginning of the video presentation.

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Sara A. Hurvitz, MD, FACP - Key Steps to Success With CDK4/6 Inhibition in Early Through Metastatic Breast Cancer: Stratification, Selection, Sequencing, and Specialty Management

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Feb 4, 2026 83:40

Endocrine-Based Therapy for HR-Positive Breast Cancer — Proceedings from a San Antonio 2025 Symposium Series

Play Episode Listen Later Jan 27, 2026 121:08

Featuring perspectives from Dr Angela DeMichele, Dr Komal Jhaveri, Dr Erica Mayer, Dr Hope S Rugo and Dr Seth Wander, including the following topics: Introduction (0:00) 1985 NCI Consensus Conference on Early Breast Cancer: Sir Richard Peto, FRS (2:01) Current Role of Genomic Assays in Treatment Decision-Making for Localized Hormone Receptor (HR)-Positive Breast Cancer — Dr DeMichele (5:13) Case: A premenopausal woman in her mid 40s with an ER-positive, HER2-negative, node-negative infiltrating ductal carcinoma (IDC) after partial mastectomy/radiation therapy who enrolls in the prospective, observational FLEX study: MammaPrint® low risk — Laurie Matt-Amaral, MD, MPH (15:30) Case: A premenopausal woman in her mid 40s after modified radical mastectomy for T2N0 ER-positive, HER2-negative IDC with an Oncotype DX® Recurrence Score (RS®) of 19 — Swati Vishwanathan, MD Case: A woman in her mid 60s with locally advanced (19 cm) ER-positive, HER2-low (IHC 1+) Stage IIIB mucinous carcinoma breast cancer and an RS of 18 — Alan B Astrow, MD (22:40) Role of CDK4/6 Inhibitors and Other Novel Strategies in Therapy for HR-Positive, HER2-Negative Localized Breast Cancer — Dr Jhaveri (30:18) Case: A woman in her mid 50s with ER-positive, HER2-negative Stage IIB, T2N1 IDC after neoadjuvant dose-dense AC-T, lumpectomy and adjuvant radiation therapy — Eleonora Teplinsky, MD (42:14) Case: A woman in her mid 60s with ER-positive, HER2-negative breast cancer with a surgically removed solitary lung metastasis after 4 years of adjuvant letrozole — Eric Fox, DO (46:32) Evolving Up-Front Treatment Paradigm for HR-Positive, HER2-Negative Metastatic Breast Cancer (mBC) — Dr Rugo (49:45) Case: A woman in her early 80s with Type 2 diabetes, well controlled hypertension and recurrent ER-positive, HER2-negative mBC after 4 years of adjuvant letrozole — Sunil Gandhi, MD (1:02:30) Clinical Utility of Agents Targeting the PI3K/AKT/mTOR Pathway for Patients with Progressive HR-Positive mBC — Dr Mayer (1:06:37) Case: A woman in her late 60s with ER-positive, HER2-low (IHC 1+), PIK3CA-mutant mBC with disease progression after 2 years of adjuvant letrozole — Laila Agrawal, MD (1:20:22) Case: A woman in her early 60s with ER-positive, HER2-low PIK3CA-mutant mBC and disease progression on first-line palbociclib/fulvestrant — Dr Teplinsky (1:26:36) Results from the Global Phase III lidERA Breast Cancer Trial of Giredestrant versus Standard Endocrine Therapy as Adjuvant Treatment for ER-Positive, HER2-Negative Localized Breast Cancer (1:31:48) Current and Future Role of Oral Selective Estrogen Receptor Degraders for Progressive HR-Positive mBC — Dr Wander (1:42:30) Case: A woman in her early 100s with locally advanced ER-positive, HER2-negative breast cancer with disease progression on letrozole, now with an ESR1 mutation — Dr Astrow (1:57:51) CME information and select publications

er positive therapy current patients md san antonio results breast cancer flex mph symposium rs proceedings cme idc endocrine inhibitors mbc her2 frs current role future role ihc cdk4 pik3ca esr1 komal jhaveri eric fox hope s rugo stage iib angela demichele stage iiib

TdC 318: Neutropenia febril - 5 Clinicagens

Ta de Clinicagem

Play Episode Listen Later Jan 21, 2026 45:52

Iaaaago Jorge convida Raphael Barreto e Lucas Brandão para discutir sobre neutropenia febril, em 5 clinicagens:1. Neutropenia febril é emergência oncológica2. Como escolher o antibiótico?3. Quando escalonar o antibiótico?4. Quando suspender o antibiótico?5. Quando prescrever filgrastim?Referências:1. Klastersky J, de Naurois J, Rolston K, et al. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016;27(suppl 5):v111-v118. doi:10.1093/annonc/mdw3252. Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update. J Clin Oncol. 2018;36(14):1443-1453. doi:10.1200/JCO.2017.77.62113. Zhang H, Wu Y, Lin Z, et al. Naproxen for the treatment of neoplastic fever: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2019;98(22):e15840. doi:10.1097/MD.00000000000158404. Zheng B, Huang Z, Huang Y, Hong L, Li J, Wu J. Predictive value of monocytes and lymphocytes for short-term neutrophil changes in chemotherapy-induced severe neutropenia in solid tumors. Support Care Cancer. 2020;28(3):1289-1294. doi:10.1007/s00520-019-04946-35. Douglas C, Morse JD, Anderson BJ. Mucositis Pain and Its Temporal Relationship to White Cell Count. Paediatr Anaesth. 2025;35(4):302-309. doi:10.1111/pan.150636. Vassallo M, Michelangeli C, Fabre R, et al. Procalcitonin and C-Reactive Protein/Procalcitonin Ratio as Markers of Infection in Patients With Solid Tumors. Front Med (Lausanne). 2021;8:627967. Published 2021 Mar 12. doi:10.3389/fmed.2021.6279677. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33(28):3199-3212. doi:10.1200/JCO.2015.62.34888. Heil G, Hoelzer D, Sanz MA, et al. A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia. The International Acute Myeloid Leukemia Study Group. Blood. 1997;90(12):4710-4718.9. Weiss JM, Csoszi T, Maglakelidze M, et al. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019;30(10):1613-1621. doi:10.1093/annonc/mdz27810. Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64(2):328-340. doi:10.7326/0003-4819-64-2-32811. Nucci M, Arrais-Rodrigues C, Bergamasco MD, et al. Management of febrile neutropenia: consensus of the Brazilian Association of Hematology, Blood Transfusion and Cell Therapy - ABHH. Hematol Transfus Cell Ther. 2024;46 Suppl 6(Suppl 6):S346-S361. doi:10.1016/j.htct.2024.11.11912. Guarana M, Nucci M, Nouér SA. Shock and Early Death in Hematologic Patients with Febrile Neutropenia. Antimicrob Agents Chemother. 2019;63(11):e01250-19. Published 2019 Oct 22. doi:10.1128/AAC.01250-1913. Rosa RG, Goldani LZ. Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrob Agents Chemother. 2014;58(7):3799-3803. doi:10.1128/AAC.02561-1414. Averbuch D, Orasch C, Cordonnier C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013;98(12):1826-1835. doi:10.3324/haematol.2013.09102515. Beyar-Katz O, Dickstein Y, Borok S, Vidal L, Leibovici L, Paul M. Empirical antibiotics targeting gram-positive bacteria for the treatment of febrile neutropenic patients with cancer. Cochrane Database Syst Rev. 2017;6(6):CD003914. Published 2017 Jun 3. doi:10.1002/14651858.CD003914.pub416. Puerta-Alcalde P, Cardozo C, Suárez-Lledó M, et al. Current time-to-positivity of blood cultures in febrile neutropenia: a tool to be used in stewardship de-escalation strategies. Clin Microbiol Infect. 2019;25(4):447-453. doi:10.1016/j.cmi.2018.07.02617. Ljungman P, Alain S, Chemaly RF, et al. Recommendations from the 10th European Conference on Infections in Leukaemia for the management of cytomegalovirus in patients after allogeneic haematopoietic cell transplantation and other T-cell-engaging therapies. Lancet Infect Dis. 2025;25(8):e451-e462. doi:10.1016/S1473-3099(25)00069-618. Maertens J, Lodewyck T, Donnelly JP, et al. Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer. Clin Infect Dis. 2023;76(4):674-682. doi:10.1093/cid/ciac62319. Aguilar-Guisado M, Espigado I, Martín-Peña A, et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017;4(12):e573-e583. doi:10.1016/S2352-3026(17)30211-9

research european blood management current cancer md treatments recommendations quando pe shock mart published fever infection medicina refer leukemia ib predictive cohorts markers aac nou quantitative optimisation prisma suppl hematology blood transfusions clinical oncology leukaemia early death infectious diseases society neutropenia jco european organization ann intern med european conference cdk4 cochrane database syst rev empiric procalcitonin naproxen clin infect dis s2352 j clin oncol medicine baltimore lancet infect dis clin microbiol infect

S14 Ep79: Medical Crossfire®: Mastering the Nuances of Early-Stage HR+/HER2- Breast Cancer—Expert Perspectives on Applying Modern Treatment Paradigms

JCO Precision Oncology Conversations

Play Episode Listen Later Jan 20, 2026 29:47

In this podcast, experts Tiffany A. Traina, MD, FASCO, Kevin Kalinsky, MD, MS, FASCO, Mark E. Robson, MD, FASCO, and Rebecca Shatsky, MD discuss data for CDK4-6 inhibitors, PARP inhibitors, and immune checkpoint inhibitors in the management of early-stage hormone receptor-positive, HER-2-negative breast cancer.

ms modern md medical treatments mastering breast cancer nuances early stage paradigms crossfire her2 parp expert perspectives cdk4 fasco kevin kalinsky mark e robson

Expanding Treatment Options for Breast Cancer: ADCs and Oral SERDs

ASCO Daily News

Play Episode Listen Later Jan 8, 2026 27:14

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

women ai los angeles france japan wisdom french travel speaker japanese er single patients treatments ucla pleasure expanding san antonio fda elevate pfizer brilliant keynote breast cancer blue sky hp oral astrazeneca trop ascent tb merck gilead novartis sg dato accommodations sanofi treatment options asco genentech adc patina her2 pfs egfr gilead sciences adcs ipsen pd l1 ild esmo thp serd tki tnbc daiichi sankyo ctdna cdk4 tkis crispr therapeutics san antonio breast cancer symposium pik3ca esr1 rugo t dxd hope rugo serds t dm1 transcript dr disclosures dr

Palbociclib in Tumors with CDKN2A Loss or Mutation

Play Episode Listen Later Jan 7, 2026 9:26

In this JCO Precision Oncology Article Insights episode, host Dr. Harold Nathan Tan summarizes "Palbociclib in Patients With Head and Neck Cancer and Other Tumors With CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study" by Worden et al. TRANSCRIPT Harold Nathan Tan: Welcome to JCO Precision Oncology Article Insights, where we explore research that is reshaping our understanding of cancer therapeutics. I'm your host, Harold Nathan Tan, and today's episode centers on the TAPUR study, an analysis that confronts a long-standing assumption in molecular oncology: namely, whether CDKN2A alterations create a therapeutic vulnerability that can be exploited by CDK4/6 inhibition with palbociclib. CDKN2A is one of the most frequently altered tumor suppressors across solid tumors. Its importance lies in its production of two proteins, p16 and p14, which serve as guardians of cell cycle progression. p16 directly inhibits CDK4 and CDK6, preventing phosphorylation of the RB protein and therefore blocking entry into S phase, whereas p14 stabilizes p53 by counteracting MDM2, enabling cells to pause or die in response to oncogenic stress. When CDKN2A is lost or mutated, these dual checkpoints collapse. CDK4/6 activity becomes unchecked, RB remains phosphorylated and inactive, and p53-mediated surveillance is blunted from a mechanistic standpoint. This creates a possible dependency on CDK4/6 signaling that could, in principle, be therapeutically reversed by palbociclib. The TAPUR study is a prospective phase 2 basket study designed to evaluate whether FDA-approved targeted agents can meaningfully benefit patients with advanced treatment-refractory cancers harboring specific genomic alterations. In this analysis, patients were eligible for palbociclib if their tumors carried CDKN2A loss or mutation and retained RB activity. Two cohorts were examined: one consisting of head and neck cancers, and another composed of a broad spectrum of tumor types that collectively shared the CDK2 alteration. The results from the head and neck cancer cohort are particularly intriguing. Among the 28 available patients, the study observed a disease control rate of 40%, surpassing the predefined threshold for a positive signal. Although the objective response rate was low at only 4% with one partial response, the durability of disease stabilization was clinically meaningful. However, the most important insight comes from examining which head and neck tumors benefited. The strongest and most durable disease control occurred in non-squamous malignancies, particularly salivary gland tumors such as adenocarcinoma, adenoid cystic carcinoma, and poorly differentiated parotid tumors, as well as in esthesioneuroblastoma. In contrast, classic head and neck squamous cell carcinoma rarely demonstrated sustained benefit. When progression-free survival was analyzed, non-squamous tumors achieved a median PFS of approximately 20 weeks compared to just eight weeks in squamous tumors. This divergence reflects deep biological differences. Many non-squamous head and neck cancers preserve an intact RB axis and rely on CDK4/6-driven cell cycle control as a core proliferative mechanism. By contrast, squamous tumors tend to accumulate a dense array of co-alterations that weaken or circumvent CDK4/6 dependency. Many squamous tumors also harbor disruptive TP53 mutations, removing essential checkpoint control and allowing the cell to bypass the growth-arresting effects of palbociclib. In other words, even though CDKN2A loss is present, CDK4/6 is no longer the dominant node controlling proliferation in these cancers, and the tumor simply finds other ways to drive cell cycle entry. One of the most thought-provoking findings from the TAPUR study involves esthesioneuroblastoma. Three patients with this rare tumor achieved durable disease control despite the lack of standardized systemic treatment options for this malignancy. Genomic analyses have shown that while esthesioneuroblastoma often carries TP53 or IDH2 mutations, a meaningful subset exhibits alterations in CDKN2A or related cell cycle regulators. The consistency of this disease stabilization observed in TAPUR may reflect a lineage-specific reliance on CDK4/6 signaling, opening the door for future exploration of CDK4/6 inhibitors in this orphan disease. In the histology-pooled cohort, which included 40 available patients across 18 tumor types, palbociclib did not achieve the disease control threshold required to declare activity, with only a disease control rate of 13% and an ORR of 5%. While a few isolated responses occurred, for instance in thymic carcinoma and B-cell lymphoma, the overall disease control rate was 13%, which failed to rise above what might be expected from the natural history of advanced refractory cancers. This outcome reinforces the principle that CDKN2A loss is not a universal predictor of CDK4/6 dependency. Many of the tumors represented in this cohort, such as pancreatic cancer, melanoma, and gastrointestinal malignancies, are well known to evolve multiple compensatory mechanisms that circumvent CDK4/6 as a critical proliferative node. The safety profile of palbociclib was consistent with its known hematologic toxicities. High rates of neutropenia, leukopenia, and thrombocytopenia were observed, along with one treatment-related death due to respiratory failure. In a setting where activity is limited to specific subgroups, these toxicities underscore the importance of careful patient selection and raise the bar for demonstrating clinically meaningful benefit, particularly in heavily pretreated populations. So what do these findings tell us about the broader landscape of precision oncology? First, they remind us that a mutation's functional role is dependent on the cellular and lineage context in which it occurs. CDKN2A loss may accelerate proliferation in many tumors, but the mechanism of that acceleration varies widely, and the degree to which a tumor relies on CDK4/6 signaling is anything but uniform. Second, the findings suggest that palbociclib monotherapy may hold meaningful and durable benefit in the subset of non-squamous head and neck cancers, particularly salivary gland malignancies and esthesioneuroblastoma. Third and perhaps most importantly, the results reinforce a growing consensus that the future of CDK4/6 inhibition in solid tumors lies not in monotherapy, but in rational combination strategies. CDK4/6 inhibitors have been shown to synergize with EGFR inhibitors, PIK3CA, and mTOR inhibitors, MEK inhibition, and even immune checkpoint blockade. These combinations aim to dismantle the compensatory pathways that allow tumors to escape CDK4/6 blockade and may unlock therapeutic potential in tumors that show limited sensitivity to monotherapy. Ultimately, the TAPUR findings challenge the notion that CDKN2A is a straightforward predictive biomarker. Instead, the study reveals CDKN2A as a biomarker whose meaning is modulated by tumor lineage, co-mutation status, and the broader regulatory circuit governing proliferation. Precision oncology must therefore move beyond single-gene interpretation towards integrated frameworks that situate genomic alterations within their biologic ecosystems. In some head and neck cancer subtypes, particularly non-squamous malignancies, that ecosystem appears amenable to CDK4/6 inhibition, and that insight, not the simplistic gene-to-drug match, represents the true value of the TAPUR analysis. Thank you for joining me for this episode of JCO Precision Oncology Article Insights. I'm Harold Nathan Tan, and I look forward to exploring more research that continues to refine how we understand and strategically exploit the vulnerabilities of cancer. 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.

loss fda rb precision tumors mutation worden asco orr genomic mtor pfs egfr mek neck cancer cdk4 tp53 pik3ca mdm2 idh2 palbociclib cdk2

Metastatic HR+ Breast Cancer SABCS 2025 Highlights: Dr. Hope Rugo

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Dec 26, 2025 23:33

Welcome to the Oncology Brothers podcast! In this episode, we dived into the key highlights from the SABCS 2025 conference, focusing on metastatic hormone receptor-positive breast cancer. Join us as we discussed: • The role of CDK4-6 inhibitors in frontline therapy, featuring updates from the AMBRE and MONALEESA-3 studies • Insights into second-line treatment options, including the VIKTORIA-1, evERA, EMBER-3, SERENA-6 trials • A critical look at the ASCENT-07 study, exploring the role of antibody-drug conjugates (ADCs) in endocrine-resistant disease We were thrilled to have Dr. Hope Rugo, a world-renowned breast medical oncologist from City of Hope, share her expertise and insights on these pivotal studies. Tune in for an informative discussion that unpacks the latest advancements in treatment options for metastatic hormone receptor-positive breast cancer, and learn how these findings may impact clinical practice. Follow us on social media: •⁠ ⁠X/Twitter: https://twitter.com/oncbrothers •⁠ ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ Don't forget to like, subscribe, and check out our other episodes for more insights on treatment algorithms, recent approvals, and conference highlights! #SABCS2025 #MBC #HRpositive #CDK46 #ADCs #OncologyBrothers

breast cancer ascent viktoria metastatic ambre adcs cdk4 highlights dr evera hope rugo monaleesa

From Resistance to Response: Evolving Treatment Pathways in HR+ Breast Cancer

Project Oncology®

Play Episode Listen Later Dec 22, 2025 4:15

Guest: Seth Wander, MD, PhD Over the past decade, CDK4/6 inhibitors have transformed the treatment landscape for HR+ breast cancer, but resistance remains a key clinical challenge. Hear from Dr. Seth Wander as he explores the latest translational insights into resistance mechanisms, including genomic alterations affecting cell cycle and signal transduction pathways, and discusses evolving therapeutic strategies. Dr. Wander is an Assistant Professor of Medicine at Harvard Medical School and the Director of Precision Medicine at the Termeer Center for Targeted Therapies at Mass General Brigham Cancer Institute. He also spoke about this topic at the 2025 San Antonio Breast Cancer Symposium.

director medicine md resistance treatments assistant professor evolving breast cancer pathways harvard medical school wander precision medicine rmd targeted therapy cdk4 reachmd san antonio breast cancer symposium conference coverage oncology and hematology global oncology academy

From Resistance to Response: Evolving Treatment Pathways in HR+ Breast Cancer

Conference Coverage

Play Episode Listen Later Dec 22, 2025 4:15

Highlights

ScienceLink

Play Episode Listen Later Dec 16, 2025 23:30

Dr. Juan Carlos Samamé, oncólogo médico de Lima, Perú, y vicepresidente de la Latin American Breast Cancer Association (LABCA), recibe al Dr. Antonio Llombart Cussac, jefe de servicio en el Hospital Arnau de Vilanova y coordinador en la Universidad Cardenal Herrera en Valencia, España. Juntos nos hablan sobre lo mejor en cáncer de mama, presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Cáncer de mama luminal:lidERA Breast Cancer [1]EPIK-B5 [2]Cáncer de mama HER2:PHERGain [3] CLEOPATRA[4]PATINA[5]HER2CLIMB-05[6]ALTTO[7]Referencias:Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial. https://sabcs.org/events/general-session-1/. Presentación científica (Abstract GS1-10). Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.De Laurentiis M., Ferreira A. M., Gligorov, J., y cols. (2025, diciembre 9–12). Alpelisib plus fulvestrant for PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer after a CDK4/6 inhibitor (EPIK-B5): Phase III, randomized, double-blind, placebo-controlled, multicenter study (Abstract RF7-02). Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Llombart-Cussac, A., Pérez-García, J., Ruiz-Borrego., y cols. Circulating tumor DNA (ctDNA) in human epidermal growth factor receptor 2-positive (HER2[+]) Early Breast Cancer (EBC): Translational analysis of PHERGain neoadjuvant tailored treatment study (Abstract GS1-06). Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Rinnerthaler, G., Gampenrieder, S. P., Pichler, A., y cols. Clinical predictors for first-line treatment duration in HER2-positive metastatic breast cancer: Results from the AGMT_MBC-Registry. AGMT_MBC-Registry study (Abstract PS5-01-04). Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Metzger, O., Mandrekar, S., & Dockter, T. (2025, December 9–12). Central nervous system outcomes from the Phase III PATINA trial (AFT-38) (Abstract RF4-01). Presentado en la San Antonio Breast Cancer Symposium (SABCS) 2025; del 09 al 12 de diciembre de 2025; San Antonio, Texas.Hamilton E., Curigliano G., Martin M., y cols (2025). HER2CLIMB-05: A randomized, double-blind, phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer. Abstract GS1-01. Presentado en el marco del Simposio de Cáncer de Mama de San Antonio 2025, celebrado del 9 al 12 de diciembre de 2025 en San Antonio, Texas, Estados Unidos.Lambertini M, Samy F, Agostinetto E y cols. Adjuvant aromatase inhibitor or tamoxifen in patients with hormone receptor-positive/HER2-positive early breast cancer: An exploratory analysis from the ALTTO (BIG 2-06) trial. Abstract #GS1-03. Presentado en la San Antonio Breast Cancer Symposium (SABCS) 2025; del 09 al 12 de diciembre de 2025; San Antonio, Texas. Abstract GS1-09.

Giredestrant Promising New Treatment For Early-Stage HR-Positive Breast Cancer

Breastcancer.org Podcast

Play Episode Listen Later Dec 11, 2025 6:41

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

positive treatments ucla breast cancer promising early stage serd bardia cdk4 san antonio breast cancer symposium aditya bardia serds

Aging-US Editors' Choice

Aging-US

Play Episode Listen Later Dec 8, 2025 3:38

The paper featured on the cover of this issue of Aging-US, published on October 30, 2025, entitled “SAMP-Score: a morphology-based machine learning classification method for screening pro-senescence compounds in p16-positive cancer cells,” represents an important methodological and conceptual advance at the interface of senescence biology, imaging and drug discovery. In this study, led by first author Ryan Wallis and corresponding author Cleo L. Bishop (Queen Mary University of London), the authors introduce SAMP-Score, a machine-learning–based framework designed to identify bona fide senescence induction in cancer cells where canonical markers fail. This is a timely and much-needed contribution to the field. Therapy-induced senescence has emerged as a powerful strategy to restrain tumor growth, yet its reliable detection in cancer cells remains a major bottleneckIn these contexts, cells often already display features associated with cellular aging, rendering conventional senescence markers ambiguous or misleading. Distinguishing true senescence from toxicity, stress responses or baseline “aged” phenotypes is therefore a critical unmet need. Rather than relying on predefined molecular readouts, the authors take a different approach and train a machine-learning model to recognize senescence-associated morphological profiles (SAMPs) which are subtle but reproducible changes in cellular architecture captured through high-content microscopy. By learning directly from image-based phenotypes, SAMP-Score is able to identify senescence with a level of precision that is difficult to achieve using marker-based strategies alone. The strength of the platform demonstrated through a large-scale screen of over 10,000 novel chemical entities in p16-positive basal-like breast cancer cells. From this screen, the compound QM5928 emerged as a robust inducer of senescence across multiple cancer models, notably without inducing cytotoxicity. Importantly, QM5928 retains activity in cellular contexts that are resistant to CDK4/6 inhibition, including palbociclib-refractory, p16-high tumors. Mechanistically, the authors show that QM5928 promotes nuclear relocalization of p16, consistent with a functional engagement of cell-cycle arrest pathways. These nuanced phenotypic changes would likely have gone undetected without the resolution and discrimination provided by SAMP-Score, underscoring the platform's ability to separate true senescence from confounding cellular states. This work exemplifies how machine learning and quantitative imaging can be harnessed to solve long-standing problems in senescence research, moving the field beyond binary marker expression toward phenotype-driven classification. Beyond its immediate relevance for cancer therapy, SAMP-Score offers a broadly applicable framework for senescence-based screening efforts across biological contexts. DOI - https://doi.org/10.18632/aging.206333 Corresponding author - Cleo L. Bishop - c.l.bishop@qmul.ac.uk Abstract video - https://www.youtube.com/watch?v=qXI_KI3EgHE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206333 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

therapy pinterest blue sky editors distinguishing doi cdk4 altmetric

Erica L. Mayer, MD, MPH - Risk Assessment and Treatment Initiation: Successfully Jumpstarting the Adjuvant CDK4/6 Inhibitor Treatment Journey in HR+, HER2- EBC

Play Episode Listen Later Dec 3, 2025 26:40

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/ARM865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until November 20, 2026.Risk Assessment and Treatment Initiation: Successfully Jumpstarting the Adjuvant CDK4/6 Inhibitor Treatment Journey in HR+, HER2- EBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

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Erica L. Mayer, MD, MPH - Nurturing Lasting Benefits of Adjuvant CDK4/6 Inhibitor Therapy in High-Risk HR+, HER2- EBC: Best Practices for Patient Education, AE Monitoring and Management, and Enhanced Adherence/Persistence

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Dec 3, 2025 22:27

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/DTQ865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until November 25, 2026.Nurturing Lasting Benefits of Adjuvant CDK4/6 Inhibitor Therapy in High-Risk HR+, HER2- EBC: Best Practices for Patient Education, AE Monitoring and Management, and Enhanced Adherence/Persistence In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

benefits management therapy patients persistence best practices nurturing monitoring lasting disclosure mayer enhanced high risk medical education adherence md mph patient education her2 inhibitor adjuvant accreditation council cdk4 pvi continuing medical education accme pharmacy education acpe practice aids peerview institute cme moc ncpd cpe aapa ipce

Erica L. Mayer, MD, MPH - Risk Assessment and Treatment Initiation: Successfully Jumpstarting the Adjuvant CDK4/6 Inhibitor Treatment Journey in HR+, HER2- EBC

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 3, 2025 26:40

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/ARM865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until November 20, 2026.Risk Assessment and Treatment Initiation: Successfully Jumpstarting the Adjuvant CDK4/6 Inhibitor Treatment Journey in HR+, HER2- EBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

Erica L. Mayer, MD, MPH - Nurturing Lasting Benefits of Adjuvant CDK4/6 Inhibitor Therapy in High-Risk HR+, HER2- EBC: Best Practices for Patient Education, AE Monitoring and Management, and Enhanced Adherence/Persistence

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 3, 2025 22:27

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/DTQ865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until November 25, 2026.Nurturing Lasting Benefits of Adjuvant CDK4/6 Inhibitor Therapy in High-Risk HR+, HER2- EBC: Best Practices for Patient Education, AE Monitoring and Management, and Enhanced Adherence/Persistence In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

Breast Cancer — Microlearning Activity 2 with Dr Priyanka Sharma: 2025 ESMO Annual Meeting Updates

Play Episode Listen Later Dec 2, 2025 14:47

Featuring an interview with Dr Priyanka Sharma, including the following topics: Patient-reported outcomes from the SERENA-6 trial of camizestrant with a CDK4/6 inhibitor for patients with HR-positive, HER2-negative advanced breast cancer and ESR1 mutations emerging during first-line endocrine-based therapy (0:00) Mayer E et al. Patient-reported outcomes (PROs) from the SERENA-6 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1m during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC). ESMO 2025;Abstract 486MO. Imlunestrant and abemaciclib versus fulvestrant and abemaciclib for ER-positive, HER2-negative advanced breast cancer: An indirect treatment comparison of 3 Phase III trials (3:00) Bidard FC et al. Imlunestrant plus abemaciclib versus fulvestrant plus abemaciclib in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC): An indirect treatment comparison (ITC) of three phase 3 trials. ESMO 2025;Abstract 496P . Giredestrant in the treatment of ER-positive, HER2-negative breast cancer: The Phase III evERA Breast Cancer and EMPRESS trials (5:39) Mayer E et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial. ESMO 2025;Abstract LBA16. Llombart-Cussac A et al. Preoperative window-of-opportunity study with giredestrant or tamoxifen (tam) in premenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) and Ki67≥10% early breast cancer (EBC): The EMPRESS study. ESMO 2025;Abstract 294MO. Capivasertib/fulvestrant as first- and second-line endocrine-based therapy for PIK3CA/AKT1/PTEN-altered HR-positive advanced breast cancer in the CAPItello-291 trial and gedatolisib/fulvestrant with or without palbociclib for HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer in the VIKTORIA-1 trial.(10:25) Rugo HS et al. Capivasertib plus fulvestrant as first and second-line endocrine-based therapy in PIK3CA/AKT1/PTEN-altered hormone receptor-positive advanced breast cancer: Subgroup analysis from the phase 3 CAPItello-291 trial. ESMO 2025;Abstract 526P. Hurvitz SA et al. Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/ HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): First results from VIKTORIA-1. ESMO 2025;Abstract LBA17. CME information and select publications

er abc patients pros primary activity breast cancer empress annual meetings cme viktoria itc wt phase iii her2 1l microlearning preoperative esmo cdk4 subgroup pik3ca priyanka sharma esr1 ki67

Patients Progressing on an AI ± CDK4/6 Inhibitors: From Biomarkers to Treatment Strategies

Keeping Current CME

Play Episode Listen Later Dec 1, 2025 31:58

Did you know that the prevalence of acquired ESR1 mutations increases after exposure to endocrine therapy? Credit available for this activity expires: 11/26/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/advancing-copd-care-through-precision-medicine-and-patient-2025a1000x00?ecd=bdc_podcast_libsyn_mscpedu

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Challenging Cases in Breast Cancer with CDK 4/6 Inhibitors – Drs. Sara Tolaney & Adam Brufsky

Play Episode Listen Later Nov 24, 2025 23:30

In this episode of the Oncology Brothers podcast, we took a deeper dive into the evolving landscape of CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer. Joined by esteemed oncologists Dr. Sara Tolaney from Dana-Farber Cancer Institute and Dr. Adam Brufsky from UPMC Hillman Cancer Center, the discussion focused on real-world scenarios involving adjuvant and metastatic settings. Key topics included: • The recent updates from the MonarchE and NATALEE trials, highlighting the approval of abemaciclib and ribociclib. • Strategies for selecting the right adjuvant treatment for high-risk patients, including dosing considerations and side effect management. • Insights into managing common toxicities associated with CDK4/6 inhibitors, such as diarrhea and QTc prolongation. • The role of CDK4/6 inhibitors in patients with visceral involvement and the implications of using these therapies in the metastatic setting. Whether you're a healthcare professional or someone interested in the latest advancements in breast cancer treatment, this episode provided valuable insights and expert opinions on navigating complex treatment decisions. Follow us on social media: •⁠ ⁠X/Twitter: https://twitter.com/oncbrothers •⁠ ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ Don't forget to subscribe for more episodes and send us your challenging cases for future discussions! #CDK4/6i #BreastCancer #MonarchE #NATALEE #Abemaciclib #Ribociclib #OncologyBrothers #HRpositive

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HR-Positive Metastatic Breast Cancer — An Interview with Dr Erika Hamilton on the Potential Role of PROTAC Estrogen Receptor Degraders (Companion Faculty Lecture)

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Play Episode Listen Later Nov 19, 2025 29:15

Featuring a slide presentation and related discussion from Dr Erika Hamilton, including the following topics: Mechanisms of endocrine resistance; incidence of ESR1 mutations in breast cancer (0:00) Testing methods for ESR1 mutations in patients with breast cancer; therapeutic options for patients with ESR1-mutant breast cancer (3:59) General overview of proteolysis-targeting chimeras (PROTACs); comparison of PROTAC estrogen receptor (ER) degraders and selective ER degraders (7:39) Early-phase data with vepdegestrant monotherapy or in combination with CDK4/6 inhibitors in ER-positive, HER2-negative metastatic breast cancer (mBC) (11:54) Phase III VERITAC-2 trial of vepdegestrant versus fulvestrant in ER-positive, HER2-negative mBC previously treated with endocrine therapy and a CDK4/6 inhibitor (17:48) Ongoing clinical trials evaluating vepdegestrant in novel combinations or treatment settings; other clinical applications of PROTACs (26:08) CME information and select publications

er positive testing faculty ongoing lecture companion mechanisms estrogen cme receptor mbc her2 metastatic breast cancer potential role cdk4 esr1 erika hamilton

EXPIRING SOON! Diagnosis and Management of Dedifferentiated Liposarcoma

Oncology Data Advisor

Play Episode Listen Later Nov 11, 2025 28:57

LAST CHANCE – Expires November 21! Dedifferentiated liposarcoma (DDLPS) poses significant challenges for diagnosis and management. In this expert‑led discussion, Dr. Richard F. Riedel (Duke University Medical Center) and Dr. Candace L. Haddox (Dana‑Farber Cancer Institute, Harvard Medical School) share practical insights on identifying MDM2/CDK4 amplification, exploring emerging treatments such as CDK4/6 inhibitors and immunotherapies, and improving outcomes through a multidisciplinary approach. Listen now and earn 0.5 CME credit: https://bit.ly/49GyP5T

S14 Ep44: Research Innovations Spark Promise for Broadening the HR+ Breast Cancer Armamentarium Post-CDK4/6 Inhibition: With Kevin Kalinsky, MD, MS, FASCO

Oncology Peer Review On-The-Go

Play Episode Listen Later Nov 7, 2025 9:39

In today's episode, we had the pleasure of speaking with Kevin Kalinsky, MD, MS, FASCO, about the evolving treatment paradigm for hormone receptor (HR)–positive breast cancer post-CDK4/6 inhibition, as well as the need for more advanced therapies to improve patient outcomes in this setting. Dr Kalinsky is a professor and director in the Division of Medical Oncology of the Department of Hematology and Medical Oncology at Emory University School of Medicine, as well as the director of the Glenn Family Breast Center and the Louisa and Rand Glenn Family Chair in Breast Cancer Research at Winship Cancer Institute in Atlanta, Georgia. In our exclusive interview, Dr Kalinsky discussed combination therapies that have shown promise for the management of HR-positive breast cancer following endocrine therapy, factors influencing treatment selection for patients who have received prior CDK4/6 inhibition, best practices for genomic testing in this population, and breast cancer research highlights from the 2025 ESMO Congress.

research ms innovation medicine md spark breast cancer broadening hematology emory university school inhibition medical oncology breast cancer research cdk4 winship cancer institute fasco kevin kalinsky

What the PATINA Trial Teaches Us About Treating HER2+ Breast Cancer

PVRoundup Podcast

Play Episode Listen Later Oct 29, 2025 9:58

Drs. Waks and Lynce review the PATINA trial, which showed that adding a CDK4/6 inhibitor to HER2-targeted and endocrine therapy improved progression-free survival in triple-positive breast cancer, shaping how this subgroup may be managed.

trial treating teaches breast cancer drs patina her2 cdk4 waks palbociclib

S1 Ep185: What Were the Key Presentations at ESMO 2025? Oncology Experts Discuss

Play Episode Listen Later Oct 27, 2025 11:31

As part of the European Society for Medical Oncology (ESMO) Congress 2025, CancerNetwork® spoke with a variety of experts about key takeaways from different late-breaking abstracts, oral presentations, and other sessions focused on potential advancements across cancer care. Presenting investigators highlighted updated results from clinical trials evaluating novel therapeutic strategies across different cancer populations, including breast cancer and lung cancer. Phase 3 VIKTORIA-1 Trial Sara A. Hurvitz, MD, FACP, the Smith Family Endowed Chair in Women's Health and senior vice president and director of the Clinical Research Division at the Fred Hutch Cancer Center, and tumor chair in breast oncology for the ONCOLOGY® editorial advisory board, first discussed findings from the phase 3 VIKTORIA-1 trial (NCT05501886). Her presentation highlighted how VIKTORIA-1 was “the first study to demonstrate a statistically significant and clinically meaningful improvement in progression-free survival [PFS] with PAM inhibition” for patients with PIK3CA wild-type advanced breast cancer. Data from the trial showed that gedatolisib plus fulvestrant (Faslodex) and palbociclib (Ibrance) produced a median PFS of 9.3 months (95% CI, 7.2-16.6) vs 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (HR, 0.24; 95% CI, 0.17-0.35; P

women university health germany phd data er medicine berlin md phase primary presenting mph harvard medical school soho mayer presentations internal medicine oncology dor viktoria orr dana farber cancer institute european society her2 pfs martin m cdk nsclc texas md anderson cancer center adcs esmo cdk4 pik3ca esr1 evera clinical research division afinitor neck medical oncology

Weight Loss Drugs and Breast Cancer

Breastcancer.org Podcast

Play Episode Listen Later Oct 21, 2025 41:25

According to a KFF poll, about one in eight, or 12%, of adults in the United States have used a GLP-1 medicine like Ozempic, Trulicity, Victoza, Mounjaro, Wegovy, or Zepbound. These drugs were originally developed to treat diabetes, but quickly started being prescribed for weight loss and other uses. While they seem like wonder drugs, GLP-1 medicines do cause side effects and have risks. Nausea, vomiting, diarrhea, and constipation are common side effects. The drugs also can cause dizziness, headaches, and elevated heartbeat. Dr. Neil Iyengar is a breast medical oncologist who studies how diet and exercise can improve quality of life for people with breast cancer. He's also prescribed GLP-1 medicines for the people he cares for. Listen to the episode to hear Dr. Iyengar explain: how GLP-1 medicines work the risks these drugs may pose for people receiving chemotherapy, immunotherapy, or a CDK4/6 inhibitor why he works closely with a weight loss specialist or endocrinologist when prescribing these medicines why the medicines work best when a person also makes lifestyle changes

united states drugs weight loss breast cancer ozempic glp wegovy nausea mounjaro iyengar zepbound kff cdk4 trulicity victoza

S14 Ep31: Metastatic Breast Cancer 2025 UPDATE

Play Episode Listen Later Oct 20, 2025 11:41

Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago. In this episode, OncLive On Air® partnered with Two Onc Docs to feature a comprehensive review of the current management of metastatic breast cancer, emphasizing evidence-based treatment strategies across molecular subtypes, toxicity management, and patient-centered care. Drs Armstrong and Tawagi discussed that the primary goals of metastatic breast cancer therapy include prolonging survival, controlling symptoms, minimizing toxicity, improving quality of life, and incorporating patients' goals and preferences into care decisions. Their discussion also highlighted the importance of recognizing when transitioning to best supportive care is most appropriate. For estrogen receptor–positive metastatic breast cancer, they noted that first-line therapy includes an aromatase inhibitor or fulvestrant (Faslodex) combined with a CDK4/6 inhibitor, with ovarian function suppression for premenopausal patients. PARP inhibitors are recommended for patients with BRCA1/2-positive disease. In visceral crisis, chemotherapy remains the category 1 recommendation. Second-line treatment options include therapies guided by repeat molecular testing. fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) is approved for patients with HER2-low disease. For HER2-positive metastatic breast cancer, first-line treatment consists of a taxane plus pertuzumab (Perjeta) and trastuzumab (Herceptin), followed by T-DXd in the second-line setting. For triple-negative metastatic breast cancer, therapy depends on PD-L1 status. The episode concluded by underscoring the role of bone-protective agents such as zoledronic acid, pamidronate, or denosumab (with dental clearance to prevent osteonecrosis). Key takeaways emphasize tailoring therapy to molecular subtype, recognizing drug-specific toxicities, and prioritizing patient-centered decision-making in the management of metastatic breast cancer.

university chicago illinois md indianapolis armstrong brca1 her2 metastatic breast cancer parp pd l1 indiana university health herceptin cdk4 enhertu t dxd

Transformative Oncology Breakthroughs and Regulatory Shifts

Pharma and BioTech Daily

Play Episode Listen Later Oct 20, 2025 5:51

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we'll delve into a series of remarkable advancements and strategic movements shaping the landscape of healthcare. Let's start with a recent spotlight on the European Society for Medical Oncology Congress 2025, where key clinical trial outcomes have emerged, potentially reshaping future treatment protocols.AstraZeneca made waves with its Phase 3 trial results for Imfinzi, a PD-L1 inhibitor, in high-risk non-muscle invasive bladder cancer. The findings suggest that Imfinzi stands strong against Pfizer's PD-1 candidate, Sasanlimab. This is particularly noteworthy as bladder cancer has historically had limited non-invasive treatment options. The implications for patient care are substantial, providing hope for improved management of this form of cancer and possibly influencing treatment standards.Meanwhile, Eli Lilly's Verzenio marked another success at the ESMO Congress with its overall survival win in early breast cancer cases. This victory enhances Verzenio's standing within the CDK4/6 inhibitor class, suggesting increased adoption in clinical settings. The demonstration of extended survival benefits not only strengthens Verzenio's competitive position but also contributes to setting a new standard of care in early breast cancer treatment.On the regulatory front, Sanofi encountered mixed outcomes from the European Medicines Agency's Committee for Medicinal Products for Human Use. While Rezurock was not recommended as a third-line treatment for chronic graft-versus-host disease, this decision underscores the stringent regulatory processes companies navigate despite existing market success in other regions like the U.S.In a significant move by the FDA to expedite drug approvals, nine companies including Merck KGaA and Regeneron received priority review vouchers. These vouchers allow a shortened review timeline, reflecting an ongoing trend towards accelerating drug availability to address unmet medical needs swiftly.In terms of strategic developments, EMD Serono—Merck KGaA's U.S. branch—has unveiled a major discount initiative for its IVF treatments on the TrumpRx platform. This aligns with broader efforts to make fertility treatments more accessible amidst rising demand and economic pressures.The metabolic dysfunction-associated steatohepatitis (MASH) arena is also witnessing robust interest with over $10 billion recently reported in mergers and acquisitions. This surge indicates confidence among Big Pharma players in MASH as a lucrative therapeutic field ripe for innovation and development.In response to competitive pressures and operational challenges, Kezar Life Sciences is preparing for layoffs following the FDA's decision to cancel a critical meeting related to its R&D program. This situation illustrates the volatile dynamics within biotech firms where regulatory decisions can significantly impact corporate strategies and workforce stability.Overall, these developments reflect an industry characterized by rapid innovation, strategic realignments, and an evolving regulatory framework. The implications for patient care are substantial as these scientific advancements promise enhanced treatment options across various therapeutic areas.Switching gears to scientific developments, Bristol Myers Squibb has reported promising results from early-stage trials of its EGFRxHER3 antibody-drug conjugate. Demonstrating a 55% overall response rate, this positions BMS to potentially gain a competitive edge in the ADC market—a sector valued for targeting cancer cells while minimizing side effects on healthy tissues.Strategic partnerships continue to shape industry growth and innovation. Roche has secured a deal with Hansoh Pharmaceutical worth up to $1.45 billion for global rights to an experimental ADC outside Greater China. SimilSupport the show

Targeting PIK3CA Mutations in HR+/HER2- Breast Cancer: New Insights from ReDiscover

Medical Industry Feature

Play Episode Listen Later Oct 17, 2025

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Sarah Sammons, MD About 40 percent of patients with metastatic HR+/HER2- breast cancer have an activating mutation in the PIK3CA gene,1,2 which plays a key role not only in tumor growth, but also in driving resistance to endocrine therapy.3-5 And while there are several FDA-approved PI3K pathway-targeted agents for patients with PIK3CA tumor mutations,6-8 they come with challenges, like modest efficacy and on-pathway effects.9-12 Given this unmet need, the ReDiscover trial evaluated the investigational agent RLY-2608 in combination with fulvestrant in in patients with PIK3CA-mutated HR+/HER2- aBC previously treated with a CDK4/6 inhibitor.13 Joining Dr. Charles Turck to share updated safety and efficacy data from the trial is Dr. Sarah Sammons, a Senior Physician at the Dana-Farber Cancer Institute and an Assistant Professor of Medicine at Harvard Medical School in Boston. References: Vasan N, Cantley LC, Vasan N, Cantley LC. At a crossroads: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy. Nat Rev Clin Oncol. 2022;19(7):471-485. doi:10.1038/s41571-022-00633-1 Network TCGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61-70. doi:10.1038/nature11412 Saal LH, Johansson P, Holm K, et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor …

nature medicine poor fda assistant professor breast cancer targeting harvard medical school comprehensive mutation rediscover pharmd new insights rmd dana farber cancer institute her2 bcps pten cdk4 pi3k reachmd pik3ca medical industry feature charles turck host charles turck

Managing Toxicities of CDK4/6 Inhibitors in Hormone Positive Breast Cancer - Dr. Stephanie Graff

managing positive hormones breast cancer toxicity detailed qt graff inhibitors cdk4

Play Episode Listen Later Oct 16, 2025 22:21

In this episode of Oncology Brothers, we dived deep into the world of CDK4-6 inhibitors, focusing on their side effects and management in breast cancer treatment. Joined by an esteemed guest, Dr. Stephanie Graff, a medical breast oncologist from Brown University Health. We explored the side effects and management strategies for three commonly used CDK4/6 inhibitors: ribociclib, abemaciclib, and palbociclib. Key topics discussed include: •⁠ ⁠The evolving role of CDK4/6 inhibitors in early breast cancer and adjuvant settings. •⁠ ⁠Detailed management of side effects such as QT prolongation, liver function tests, and diarrhea. •⁠ ⁠The importance of shared decision-making with patients regarding treatment options. •⁠ ⁠Insights into the latest clinical trial data and its implications for practice. Whether you're a healthcare professional or someone interested in oncology, this episode provides valuable insights into optimizing patient care while managing the complexities of CDK4-6 inhibitors. Follow us on social media: •⁠ ⁠X/Twitter: https://twitter.com/oncbrothers •⁠ ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ Don't forget to like, subscribe, and check out our other episodes for more discussions on oncology treatments and patient management strategies! #CDK4/6inhibitors #BreastCancer #Ribociclib #Abemaciclib #Palbociclib #OncologyBrothers #SideEffectManagement #HRpositiveBC

A Patient-Centered Approach to CDK4/6 Inhibitors

Cancer Buzz

Play Episode Listen Later Oct 8, 2025 4:49

The George Washington Cancer Center serves a racially, ethnically, and socioeconomically diverse population across Washington, D.C., northern Virginia, and southern Maryland. Their Breast Cancer Program has found that a community-informed model is most successful for managing care and adverse events related to CDK4/6 inhibitors. In this episode, CANCER BUZZ speaks with Pavani Chalasani, MD, MPH, director of the division of hematology/oncology at the George Washington University Cancer Center about the flexible and collaborative team design that allows for culturally responsive and comprehensive care for their patients with breast cancer. Pavani Chalasani, MD, MPH Director, Division of Hematology/Oncology George Washington University Cancer Center Washington, DC “I think adapting and knowing what the barriers are and how we can divide and support and come up with roles for our team members is essential.” “[Navigators] give us an understanding of where the hesitancy is coming from, or where the concerns are coming from, so that we can do a better job explaining and overcoming those barriers.” Resources · Spotlight on George Washington (GW) Cancer Center: Managing Adverse Effects of CDK4/6 Inhibitors With a Patient-Centered, Team-Based Approach · ACCC Resource: CDK4/6 Inhibitors Management · ACCC CDK4/6 Inhibitors Infographic

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Triple Threat: Key Data on Simultaneous Estrogen, CDK4/6, and PI3K Inhibition in mBC

ReachMD CME

Play Episode Listen Later Oct 7, 2025

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Triple-Threat-Key-Data-on-Simultaneous-Estrogen-CDK4-6-and-PI3K-Inhibition-in-mBC/37335/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

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Triple Threat: Key Data on Simultaneous Estrogen, CDK4/6, and PI3K Inhibition in mBC

ReachMD CME

Play Episode Listen Later Oct 7, 2025

data testing threats bc triple threat estrogen cme simultaneous rmd mbc inhibition her2 cdk4 pi3k reachmd cme/ce pik3ca

Postmastectomy Radiation Therapy: ASTRO-ASCO-SSO Guideline

ASCO Guidelines Podcast Series

Play Episode Listen Later Sep 16, 2025 15:38

Dr. Kathleen Horst, Dr. Rachel Jimenez, and Dr. Yara Abdou discuss the updated guideline from ASTRO, ASCO, and SSO on postmastectomy radiation therapy. They share new and updated recommendations on topics including PMRT after upfront surgery, PMRT after neoadjuvant systemic therapy, dose and fractionation schedules, and delivery techniques. They comment on the importance of a multidisciplinary approach and providing personalized care based on individual patient characteristics. Finally, they review ongoing research that may impact these evidence-based guidelines in the future. Read the full guideline, “Postmastectomy Radiation Therapy: An ASTRO-ASCO-SSO Clinical Practice Guideline” at www.asco.org/breast-cancer-guidelines" TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-01747 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Kathleen Horst, expert panel chair from Stanford University; Dr. Rachel Jimenez, expert panel vice chair from Massachusetts General Hospital; and Dr. Yara Abdou, ASCO representative from the University of North Carolina, authors on "Postmastectomy Radiation Therapy: An American Society for Radiation Oncology, American Society of Clinical Oncology, and Society of Surgical Oncology Clinical Practice Guideline." Thank you for being here today, Dr. Horst, Dr. Jimenez, and Dr. Abdou. Dr. Kathleen Horst: Thank you for having us. Brittany Harvey: And then just before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Horst, Dr. Jimenez, and Dr. Abdou who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. Then to dive into the content that we are here today to talk about, Dr. Horst, could you start us off by describing what prompted the update for this joint guideline between ASTRO, ASCO, and SSO, and what is the scope of this 2025 guideline on postmastectomy radiation therapy? Dr. Kathleen Horst: Thank you. This joint guideline was last updated in 2016. Over the past decade, the treatment of breast cancer has evolved substantially. Newer systemic therapy regimens have increasingly personalized treatment based on tumor biology, and local therapy management has explored both the de-escalation of axillary surgery and more abbreviated courses of radiation therapy. Given these advances, it was important to revisit the role of postmastectomy radiotherapy in this modern era of breast cancer therapy. This updated guideline addresses four key questions, including postmastectomy radiation therapy after upfront surgery as well as after neoadjuvant systemic therapy. It also reviews the evolving role of various dose and fractionation schedules and optimal treatment techniques and dose constraints. Brittany Harvey: Excellent. I appreciate that background, Dr. Horst. So then, next, Dr. Jimenez, I would like to review the recommendations of this guideline across those four key questions that Dr. Horst just mentioned. So first, what does the panel recommend for PMRT for patients who received initial treatment with mastectomy? Dr. Rachel Jimenez: The panel provided pretty strong consensus that patients with positive lymph nodes or patients with large tumors involving the skin or the chest wall should receive postmastectomy radiation. However, the panel also recognized that the omission of postmastectomy radiation may be appropriate for select patients who have positive lymph nodes and have an axillary lymph node dissection if they have a low nodal burden and other favorable clinical or pathologic features. For patients without lymph node involvement at the time of surgery and no involvement of the skin or chest wall, postmastectomy radiation was not advised by the panel. Brittany Harvey: Understood. It is helpful to understand those recommendations for that patient population. Following that, Dr. Abdou, what are the key recommendations for PMRT for patients who received neoadjuvant systemic therapy before mastectomy? Dr. Yara Abdou: When we think about PMRT after neoadjuvant treatment, the key point is that the initial stage of presentation still matters a lot. So for example, if a patient comes in with more advanced disease, say a large primary tumor, like a clinical T4, or more extensive nodal disease, like an N2 or N3 disease, those patients should get PMRT, no matter how well they respond to neoadjuvant therapy, because we know it reduces the risk of recurrence and that has been shown pretty consistently. On the other hand, if there are still positive lymph nodes after neoadjuvant treatment, basically residual nodal disease, PMRT is also strongly recommended because the risk of local-regional recurrence is much higher in that setting. The gray area is the group of patients who start with a lower burden of nodal disease, such as N1 disease, but then become node negative at surgery. For those patients, we tend to individualize the decision. So if the patient is young or has triple-negative disease, or if there is a lot of residual disease in the breast even though the nodes are cleared, then radiation is probably helpful. But if everything has melted away with pCR in both the breast and the nodes, then it may be safe to omit PMRT in those patients. For patients with smaller tumors and no nodal involvement to begin with, like a clinical T1-T2 N0, if they are still node negative after neoadjuvant treatment, then PMRT is generally not recommended because their baseline recurrence risk is low. And finally, if the margins are positive and cannot be re-excised, then PMRT is recommended after neoadjuvant therapy. Brittany Harvey: Yes, those distinctions are important for appropriate patient selection. So then, Dr. Horst, we have just reviewed the indications for PMRT, but for those patients who receive PMRT, what are the appropriate treatment volumes and dose fractionation regimens? Dr. Kathleen Horst: The guideline addresses coverage of the chest wall and regional nodes with a specific discussion of the data regarding internal mammary nodal irradiation, which has been an area of controversy over many years. The guideline also reviews the data exploring moderate hypofractionation, or shorter courses of radiation therapy. The task force recommends utilizing moderate hypofractionation for the majority of women requiring postmastectomy radiation, which is likely to have a large impact on clinical practice. This recommendation is based on the evolving data demonstrating that a 3-week course of radiotherapy after mastectomy provides similar oncologic outcomes and minimal toxicity for most patients compared to the standard 5-week treatment course. Brittany Harvey: Thank you for reviewing that set of recommendations as well. So then, Dr. Jimenez, to wrap us up on the key questions here, what delivery techniques are recommended for treating patients who receive PMRT? Dr. Rachel Jimenez: So this portion of the guideline is likely to be most helpful for radiation oncologists because it represents the most technical part of the guideline, but we do believe that it offers some important guidance that has, to this point, been lacking in the postmastectomy radiation setting. So first, the panel recommends that all patients should undergo 3-dimensional radiation planning using CAT scan based imaging, and this includes contouring. So contouring refers to the explicit identification, using a drawing interface on the CAT scan imaging, by the radiation oncologist to identify the areas that are targeted to receive radiation, as well as all of the nearby normal tissues that could receive unintended radiation exposure. And we also provide radiation oncologists in the guideline with suggestions about how much dose each target tissue should receive and what the dose limits should be for normal tissues. Additionally, we make some recommendations regarding the manner in which radiation is delivered. So for example, we advise that when conventional radiation methods are not sufficient for covering the areas of the body that are still at risk for cancer, or where too high of a dose of radiation would be anticipated to a normal part of the body, that providers employ a technique called intensity modulated radiation therapy, or IMRT. And if IMRT is going to be used, we also advise regular 3-dimensional imaging assessments of the patient's body relative to the treatment machine to ensure treatment fidelity. When the treatments are delivered, we further advise using a deep inspiration breath-hold technique, which lowers the exposure to the heart and to the lungs when there is concern for cardiopulmonary radiation exposure, and again, that image guidance be used along with real-time monitoring of the patient's anatomy when those techniques are employed. And then finally, we advise that patients receiving postmastectomy radiation utilize a bolus, or a synthetic substance placed on the patient's skin to enhance radiation dose to the superficial tissue, only when there is involvement of the skin with cancer or other high-risk features of the cancer, but not for every patient who receives postmastectomy radiation. Brittany Harvey: Understood. And then, yes, you just mentioned that section of the guideline is probably most helpful for radiation oncologists, but I think you can all comment on this next question. What should all clinicians, including radiation oncologists, surgical oncologists, medical oncologists, and other oncologic professionals, know as they implement all of these updated recommendations? Dr. Rachel Jimenez: So I think one of the things that is most important when we consider postmastectomy radiation and making recommendations is that this is a multidisciplinary panel and that we would expect and encourage our colleagues, as they interpret the guidelines, to employ a multidisciplinary approach when they are discussing each individual patient with their surgical and medical oncology colleagues, that there is no one size fits all. So these guidelines are intended to provide some general guidance around the most appropriate techniques and approaches and recommendations for the utilization of postmastectomy radiation, but that we recognize that all of these recommendations should be individualized for patients and also represent somewhat of a moving target as additional studies, both in the surgical and radiation oncology realm as well as in the systemic therapy realm, enter our milieu, we have to adjust those recommendations accordingly. Dr. Kathleen Horst: Yeah, I would agree, and I wanted to comment as a radiation oncologist, we recognize that local-regional considerations are intertwined with systemic therapy considerations. So as the data evolve, it is critical to have these ongoing updates in a cross-disciplinary manner to ensure optimal care for our patients. And as Dr. Jimenez mentioned, these multidisciplinary discussions are critical for all of us to continue to learn and understand the evolving recommendations across disciplines but also to individualize them according to individual patients. Dr. Yara Abdou: I could not agree more. I think from a medical oncology perspective, systemic therapy has gotten much better with adjuvant CDK4/6 inhibitors, T-DM1, capecitabine, and immune therapy. So these are all newer adjuvant therapies, so the baseline recurrence risks are lower than what they were in the trials that established PMRT. So the absolute benefit of radiation varies more now, so smaller for favorable biology but still relevant in aggressive subtypes or with residual disease. So it is definitely not a one-size-fits-all. Brittany Harvey: Yes, I think it is important that you have all highlighted that multidisciplinary approach and having individualized, patient-centric care. So then, expanding on that just a little bit, Dr. Abdou, how will these guideline recommendations affect patients with breast cancer? Dr. Yara Abdou: So basically, reiterating what we just talked about, these guidelines really move us towards personalized care. So for patients at higher risk, so those with larger tumors, multiple positive nodes, or residual nodal disease after neoadjuvant therapy, PMRT remains essential, consistently lowering local-regional recurrence and improving survival. But for patients at intermediate or lower risk, the recommendations support a more selective approach. So instead of a blanket rule, we now integrate tumor biology, response to systemic therapy, and individual patient factors to decide when PMRT adds meaningful benefit. So the impact for patients is really important because those at high risk continue to get the survival advantage of radiation while others can be spared the unnecessary treatment and side effects. So in short, we are aligning PMRT with modern systemic therapy and biology, making sure each patient receives the right treatment for their situation. Brittany Harvey: Absolutely. Individualizing treatment to every patient will make sure that everyone can achieve the best outcomes as possible. So then, Dr. Jimenez, to wrap us up, I believe Dr. Horst mentioned earlier that data continues to evolve in this field. So in your opinion, what are the outstanding questions regarding the use of PMRT and what are you looking to for the future of research in this space? Dr. Rachel Jimenez: So there are a number of randomized phase III clinical trials that are either in active accrual or that have reported but not yet published that are exploring further de-escalation of postmastectomy radiation and of axillary surgery. And so we do not yet have sufficient data to understand how those two pieces of information integrate with each other. So for example, if you have a patient who has a positive lymph node at the time of diagnosis and forgoes axillary surgery aside from a sentinel lymph node biopsy, we do not yet know that we can also safely forgo radiation entirely in that setting. So we expect that future studies are going to address these questions and understand when it is appropriate to simultaneously de-escalate surgery and radiation. Additionally, there is a number of trials that are looking at ways in which radiation could be omitted or shortened. So there is the RT CHARM trial, which has reported but not yet published, looking at a shorter course of radiation. And so we do make recommendations around that shorter course of radiation in this guideline, but we anticipate that the additional data from the RT CHARM study will provide further evidence in support of that. Additionally, there is a study called the TAILOR RT trial, which looks at forgoing postmastectomy radiation in patients who, to Dr. Abdou's point, have a favorable tumor biology and a low 21-gene recurrence score. And so we are going to anticipate the results from that study to help guide who can selectively forgo postmastectomy radiation when they fall into that favorable risk category. So there are a number of questions that I think will help flesh out this guideline. And as they publish, we will likely publish a focused update on that information to help provide context for our colleagues in the field and clarify some of these recommendations to suit the latest data. Brittany Harvey: Absolutely. We will look forward to those de-escalation trials and ongoing research in the field to build on the evidence and look for future updates to this guideline. So I want to thank you for your work to update these guidelines, and thank you for your time today, Dr. Horst, Dr. Jimenez, and Dr. Abdou. Dr. Rachel Jimenez: Thank you. Dr. Yara Abdou: Thank you. Dr. Kathleen Horst: Thank you. Brittany Harvey: And then finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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.

Managing CDK4/6 Inhibitor Toxicities in Breast Cancer

Cancer Buzz

Play Episode Listen Later Sep 2, 2025 8:29

Effective management of adverse events and addressing barriers to care are critical to optimizing outcomes and maintaining quality of life for patients receiving CDK4/6 inhibitors. In this episode, CANCER BUZZ speaks with Julia Lea Ziegengeist, PharmD, BCOP, clinical pharmacist coordinator in solid tumor oncology at Atrium Health Levine Cancer Institute about proactive, team-based strategies to identify, monitor, and manage treatment-related toxicities in patients with early-stage and metastatic HR-positive, HER2-negative breast cancer. Dr. Ziegengeist sheds light on the patient journey, the roles of various multidisciplinary care team members, and useful resources for language and literacy barriers. “I think the biggest thing that is specific to CDK4/6 inhibitors is... eligibility criteria and when we're using the drugs in what setting, having those monitoring protocols and getting that multidisciplinary collaboration is really key.” – Julia Lea Ziegengeist, PharmD, BCOP Julia Lea Ziegengeist, PharmD, BCOP Clinical Pharmacist Coordinator, Solid Tumor Oncology  Levine Cancer Institute  Atrium Health  Charlotte, NC  Resources: ACCC Resource: CDK4/6 Inhibitors Management ACCC CDK4/6 Inhibitors Infographic

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How to Use CDK4/6 Inhibitors in Breast Cancer

Healthcare Unfiltered

Play Episode Listen Later Aug 29, 2025 9:05

Dr. Virginia Kaklamani, world renowned breast cancer specialist and researcher, visits with Healthcare Unfiltered EXPRESS to detail how this class of agents are used in metastatic and early stage breast cancer. A perfect guide for all clinicians.

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Racial and Ethnic Disparities Among Medicare Beneficiaries

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Aug 28, 2025 28:43

Host Davide Soldato and guest Dr. John K. Lin discuss the JCO article "Racial and Ethnic Disparities Along the Treatment Cascade Among Medicare Fee-For-Service Beneficiaries with Metastatic Breast, Colorectal, Lung, and Prostate Cancer." TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Davide Soldato: Hello, and welcome to JCO After Hours, the podcast where we sit down with authors of the latest articles published in the Journal of Clinical Oncology. I'm your host, Dr. Davide Soldato, a medical oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by Dr. Lin, assistant professor in the Department of Health Services Research at the University of Texas MD Anderson Cancer Center. Dr. Lin and I will be discussing the article titled, "Racial and Ethnic Disparities Along the Treatment Cascade Among Medicare Fee-for-Service Beneficiaries With Metastatic Breast, Colorectal, Lung, and Prostate Cancer." Thank you for speaking with us, Dr. Lin. Dr. Lin: Thank you so much for having me. I appreciate it. Dr. Davide Soldato: So, just to start, to frame a little bit the study, I just wanted to ask you what prompted you and your team to look specifically at this question - so, racial and ethnic disparities within this specific population? And related to this question, I just wanted to ask how this work is different or builds on previous work that has been done on this research topic. Dr. Lin: Yeah, absolutely. Part of the impetus for this study was the observation that despite people who are black or Hispanic having equivalent health insurance status - they all have Medicare Fee-for-Service - we've known that treatment and survival differences and disparities have persisted over time for patients with metastatic breast, colorectal, lung, and prostate cancer. And so, the question that we had was, "Why is this happening, and what can we do about it?" One of the reasons why eliminating racial and ethnic disparities in survival among Medicare beneficiaries with metastatic cancer has been elusive is because these disparities are occurring along a lot of dimensions. Whether or not it's because the patient presented late and has very extensive metastatic cancer; whether or not the patient has had a difficult time even seeing an oncologist; whether or not the patient has had a difficult time starting on any systemic therapy; or maybe it's because the patient has had a difficult time getting guideline-concordant systemic therapy because, more recently, these treatments have become so expensive. Disparities, we know, are occurring along all of these different facets and areas of the treatment cascade. Understanding which one of these is the most important is the key to helping us alleviate these disparities. And so, one of our goals was to evaluate disparities along the entire treatment cascade to try to identify which disparities are most important. Dr. Davide Soldato: Thank you very much. That was very clear. So, basically, one of the most important parts of the research that you have performed is really focusing on the entire treatment cascade. So, basically, starting from the moment of diagnosis up to the moment where there was the first line of treatment, if this line of treatment was given to the patient. So, I was wondering a little bit, because for this type of analysis, you used the SEER-Medicare linked database. So, can you tell us a little bit which was the period of time that you selected for the analysis? Why do you think that that was the most appropriate time to look at this specific question? And whether you feel like there is any potential limitation in using this type of database and how you handled this type of limitations? Dr. Lin: Yeah, absolutely. It's a great question. And I want to back up a little bit because I want to talk about the entire treatment cascade because I think that this is really important for our research and for future research. We weren't the first people to look at along the treatment cascade for a disease. Actually, this idea of looking along the treatment cascade was pioneered by HIV researchers and has been used for over a decade by people who study HIV. And there are a lot of parallels between HIV and cancer. One of them is that with HIV, there are so many areas along that entire treatment cascade that have to go right for somebody's treatment to go well. Patients have to be diagnosed early, they have to be given the right type of antiretrovirals, they have to be adherent to those antiretrovirals. And if you have a breakdown in any one of those areas, you're going to have disparities in care for these HIV patients. And so, HIV researchers have known this for a long time, and this has been a big cornerstone in the success of getting people with HIV the treatment that they need. And I think that this has a lot of parallels with cancer as well. And so, I am hoping that this study can serve as a model for future research to look along the entire treatment cascade for cancer because cancer is, similarly, one of these areas that requires multidisciplinary, complex medical care. And understanding where it is breaking down, I think, is crucial to us figuring out how we can reduce disparities. But for your question about the SEER-Medicare linked database, so we looked between 2016 and 2019. That was the most recent data that was available to us. And one of the reasons why we were excited to look at this is because there were some new treatments that were just released and FDA-approved around 2018, which we were able to study. And this included immunotherapy for non–small cell lung cancer, and then it also included androgen receptor pathway inhibitors, the second-generation ones, for prostate cancer. And the reason why this is important is because for some time, as we have developed these new therapies, there's been a lot of concern that there have been disparities in access to these novel therapies because of how expensive they are, particularly for the Medicare population. And so one of the reasons why we looked specifically at this time period was to understand whether or not, in more recent years, these novel therapies, people are having increasing disparities in them and whether or not increasing disparities in these more expensive, newer therapies is contributing to disparities in mortality. That being said, obviously, we're in 2025 and these data are by now six years old, and so there are additional therapies that are now available that weren't available in the past. But I think that, that being said, at least it's sort of a starting point for some of the more important therapies that have been introduced, at least for non–small cell lung cancer and prostate cancer. And the database, SEER-Medicare, is helpful because it uses the population cancer registry, which is the SEER registry cancer registry, linked to Medicare claims. So, any type of medical care that's billed through Medicare, which is going to basically be all of the medical care that these patients receive, for the most part, we're going to be able to see it. And so, I think that this is a really powerful database which has been used in a lot of research to understand what kind of care is being received that has been billed through Medicare. So, one of the limitations with this database is if there is care that's received that was not billed through Medicare, we're not going to be able to see that. And this does not happen probably that frequently, particularly because most patients who have insurance are going to be receiving care through insurance. However, we may see it for some of the oral Part D drugs. Some of those drugs are so expensive that patients cannot pay for the coinsurance during that time. And it's possible that some of those drugs patients were getting for free through the manufacturer. We potentially missed some of that. Dr. Davide Soldato: So, going a little bit into the results, I think that these are very, very interesting. And probably the most striking one is that when we look at the receipt of any type of treatment for metastatic breast, colorectal, prostate, and lung cancer - and specifically when we look at guideline-directed first-line treatments - you observed striking differences. So, I just wanted you to guide us a little bit through the results and tell us a little bit which of the numbers surprised you the most. Dr. Lin: So, what we were expecting is to see large disparities in receiving what we called guideline-directed systemic therapy. And guideline-directed systemic therapy during this time kind of depended on the cancer. So, we thought that we were going to see large disparities in guideline-directed therapy because these were the more novel therapies that were approved, and thus they were going to be the more expensive therapies. And so, what this meant was for colorectal cancer, this was going to be any 5-FU–based therapy. For lung cancer, this was going to be any checkpoint inhibitor–based therapy. For prostate cancer, this was going to be any ARPI, so this was going to be things like abiraterone or enzalutamide. And for breast cancer, this was going to be CDK4 and 6 TKIs plus any aromatase inhibitor. And so, for instance, for breast, prostate, and lung cancer, these were going to be including more expensive therapies. And so, what we expected to see was large disparities in receiving some of these more expensive, novel therapies. And we thought we were going to see fewer disparities in receiving some of the cheaper therapies, such as aromatase inhibitors, 5-FU, older platinum chemotherapies for lung cancer, and ADT for prostate cancer. We were shocked to find that we saw large racial and ethnic disparities in seeing some of the older, cheaper chemotherapies and hormonal therapies. So for instance, for breast cancer, 59% of black patients received systemic therapy, whereas 68% of white patients received systemic therapy. For colorectal, only 23% of black patients received any systemic therapy versus 34% of white patients. For lung, only 26% of black patients received any therapy, whereas 39% of white patients did. And for prostate, only 56% of black patients received any systemic therapy versus 77% of white patients. And so, we were pretty shocked by how large the disparities were in receiving these cheap, easy-to-access systemic therapies. Dr. Davide Soldato: Thank you very much. So, I just wanted to go a little bit deeper in the results because, as you said, there were striking differences even when we looked at very old and also cheap treatments that, for the majority of the patients that were included inside of your study, were actually basically available for a very small price to these patients who had the eligibility for Medicare or Medicaid. And I think that one of the very interesting parts of the research was actually the attention that you had at looking how much of these disparities could be explained by several factors. And actually, one of the most interesting results is that you observed that low-income subsidy status was actually a big determinant of these disparities in terms of treatment. So, I just wanted to guide us a little bit through these results and then just your opinion about how these results should be interpreted by policymakers. Dr. Lin: Yeah, absolutely. I'm going to explain a little bit about what low-income subsidy status is and dual-eligibility status. Some of the listeners may not know what low-income subsidy status or dual-eligibility status is. Low-income subsidy status is part of Medicare Part D. Medicare Part D is an insurance benefit that allows patients to receive oral drugs. So these are drugs that are dispensed through the pharmacy, such as the CDK4/6 inhibitors, as well as second-generation ARPIs in our study. For patients who have Medicare Part D and whose income is low enough - falls below a certain federal poverty level threshold - those patients will receive their oral drugs for much cheaper. And this is really important for some of these more novel therapies because for some of these more novel therapies, if you don't have low-income subsidy status, you may be paying thousands of dollars for a single prescription of those drugs. Whereas if you have low-income subsidy status, you may be paying less than $10. And so that difference, greater than $1,000 or $2,000 versus less than $10, one would think that the patient who's paying less than $10 would be much more likely to receive those therapies. So that's low-income subsidy status. Low-income subsidy status, importantly, doesn't apply for infused medications like immunotherapy. But it's important to know that most people with low-income subsidy status - about 88% - are also dual-eligible. What dual-eligible means is that they have both Medicare and Medicaid. Medicare being the insurance that everybody has in our study who's greater than 65. And Medicaid is the state-run but federally subsidized insurance that patients with low incomes have. And so patients who are dual-eligible - and about 87% of those with low-income subsidy status are dual-eligible - those patients have both Medicaid and Medicare, and they basically pay next to nothing for any of their medical care. And that's because Medicare will reimburse most of the medical care and the copays or coinsurance are going to be covered by Medicaid. So Medicaid is going to pick up the rest of the bill. So, most of the patients who have low-income subsidy status who are dual-eligible, these patients pay almost nothing for their medical care - Part B or Part D, any of their drugs. And so, one would expect that if cost were the main determinant of disparities in cancer care, then one would expect that dual-eligibles, most of them would be receiving treatment because they're facing minimal to no costs. What we found is that when we broke down the racial and ethnic disparity by a number of factors - including LIS status/dual eligibility, age, the number of comorbidities, etcetera - what we found was that the LIS or dual-eligibility status explained about 20% to 45% of the disparities that we saw in receiving treatment. And what that means is despite these patients paying next to nothing for their drugs, these are the most likely patients to not be treated for their cancer at all. So they're most likely to basically be diagnosed, survive for two months, see an oncologist, and then never receive any systemic therapy for their cancer. And this is not just chemotherapies for colorectal or lung cancer. This includes cheaper, easier-to-tolerate hormonal therapies that you can just take at home for breast cancer, or you can get every six months for prostate cancer, that people who even have poorer functional status are able to take. However, for whatever reason, these dual-eligible or LIS patients are very unlikely to receive treatment compared to any other patient. The low likelihood of treating this group of patients, that explains a large portion of the racial and ethnic disparities that we see. Dr. Davide Soldato: And one thing that I think is very interesting and might be of potential interest to our listeners is, did you compare survival outcomes in these different settings? And did you observe any significant differences in terms of racial and ethnic disparities once you saw that there was a significant difference when looking at both receipt of any type of treatment and also guideline-directed treatments? Dr. Lin: We saw that there were large disparities in survival by race and ethnicity when you look overall. However, when you just account for the patients who received any systemic therapy at all - not just guideline-directed systemic therapy - those differences in survival essentially disappeared. And so, what that suggests is that if black patients were just as likely to receive any systemic therapy at all as white patients, we would expect that the survival differences that we were seeing would disappear. And this is not even just looking at guideline-directed systemic therapy. This was looking just at systemic therapy alone. And so, while guideline-directed systemic therapy should be a goal, our research suggests that if we are to close the gap in disparities in overall survival among black and white patients, we must first focus on patients just receiving any type of treatment at all. And that should be the very first focus that policymakers, that leaders in ASCO, that health system leaders, that physicians, that we should focus on: just trying to get any type of treatment to our patients who are poorer or black. Dr. Davide Soldato: Thank you very much. And this was not directly related to the research that you performed, but going back to this very point - so, increasing the number of patients that receive any kind of systemic treatment before looking at guideline-directed treatments - what would you feel would be the best way to approach this in order to decrease the disparities? Would you look at interventions such as financial navigation or maybe improving referral pathways or providing maybe more culturally adapted information to the patients? Because in the end, what we see is disparities based on racial and ethnicity. We see that we can reduce these disparities if we get these patients to the treatment. But in the end, what would you feel is the best way to bring patients to these types of treatments? Dr. Lin: I think the most important thing is to understand that these disparities are not primarily happening because of the high cost of cancer treatment. These disparities are happening because of other social vulnerabilities that these patients are facing. And so these vulnerabilities could be a lot of things. It could be mistrust of the medical system. It could be fear of chemotherapy or other treatments. It could be difficulty taking time off of work. It could be any number of things. What we do know is when we've looked at the types of interventions that can help patients receive treatment, navigation is probably the most effective one. And the reason why I think that is because when patients don't receive treatment because of social vulnerability, I sort of look at social vulnerability like links in a chain. Any weakest link is going to result in the patient not receiving treatment. This may be because they have a hard time taking time off of work. This may be because they had a hard time getting transportation to their physician. It may be because they had an interaction with a physician, but that interaction was challenging for the patient. Maybe they mistrusted the physician. Maybe they're worried about the medical system. If any of these things goes wrong, the patient is not going to be treated. The patient navigator is the only person who can spot any of those weak links within the chain and address them. And so, I think that the first thing to do is to get patient navigation systems in place for our vulnerable patients throughout the United States. And this is incredibly important because in Medicare, patient navigation is reimbursable. And so this is not something that's ‘pie in the sky'. This is something that's achievable today. The second thing is that it's really important that we see these vulnerabilities happening for patients who are dual-eligible, who have both Medicare and Medicaid. One of the reasons why this is important is because there has been a lot of research outside of what we've done that has shown vulnerabilities for dual-eligible patients who have Medicare for a number of different diseases. And the reason why is because, although patients are supposed to have the benefits of both Medicare and Medicaid, usually these two insurances do not play nicely together. It creates a huge, bureaucratic, complex mess and maze that most of these patients are unable to navigate. And so many of these patients are unable to actually receive the full reimbursement from both Medicare and Medicaid that they should be getting because those two insurers are not communicating well. And so the second thing is that national cancer organizations need to be supporting policies and legislation that is already being discussed in Congress to revamp the dual-eligible system so that it facilitates these patients getting properly reimbursed for their care from both Medicare and Medicaid and these systems working together well. The third thing is that Medicaid itself has many benefits that can allow patients to receive care, like they have transportation benefits so that patients can get to and from their doctor's appointments with ease. And so I think this will be additionally very, very helpful for patients. The last thing is, you know, it's possible that future innovations such as telemedicine and tele-oncology and cancer care at home can also make it easier for some of these patients who may be working a lot to receive care. But what I would say is that our study should be a call for healthcare delivery researchers to start piloting interventions to be able to help these patients receive systemic therapy. And so what this could look like is trying to get that care navigation and implement that in clinics so that patients can be receiving the care that they need. Dr. Davide Soldato: Thank you very much. That was a very clear perspective on how we can tackle this issue. So, I just wanted to close with a sort of personal question. I was wondering what led you to work specifically in this research field that is very challenging, but I think it's particularly critical in healthcare systems like in the United States. Dr. Lin: Yeah, absolutely. One of the most important things for me as an oncologist and a researcher is being able to know that all patients in the United States - and obviously abroad - who have cancer should be able to receive the kind of care that they deserve. I don't think that patients, because their incomes are lower or because their skin looks a certain color or because they live in rural areas, these shouldn't be determinants of whether or not cancer patients are receiving the care that they need. We can develop and pioneer the very best treatments and breakthroughs in oncology, but if our patients are not receiving them - if only 20% of our patients with colon cancer or lung cancer are receiving any type of systemic therapy, who are black - this is a big problem. But this is something that I think that our system can tackle. We need to get these breakthroughs that we have in oncology to every single cancer patient in America and every single cancer patient in the world. I think this is a goal that all oncologists should have, and I think that this is something that, honestly, is achievable. I think that research is a powerful tool to give us a lens into understanding exactly why it is that certain patients are not getting the care that they deserve. And my goal is to continue to use research to shed light on why our system is not performing the way that we all want it to be. Dr. Davide Soldato: Circling back to your research, actually the manuscript that was published was supported by a Young Investigator Award by the American Society of Clinical Oncology. So, was this the first step of a more broad research, or do you have any further plans to go deeper in this topic? Dr. Lin: Yeah, absolutely. First, I want to thank the ASCO Young Investigator Award for funding this research because I think it's fair to say that this research would not have happened at all without the support of the ASCO YIA. And the fact that ASCO is doing as much as it can to support the future generation of cancer researchers is incredible. And it's a huge resource, and having it come at the time that it did is critical for so many of us. So I think that this is an unbelievable thing that ASCO does and continues to do with all of its partners. For me, yeah, this is definitely a stepping stone to further research. Medicare Fee-for-Service is only one part of the population. I want to spread this research and extend it to patients who have other types of insurances, look at other types of policies, and also try to conduct some of the cancer care delivery research that's needed to try to pilot some interventions that can resolve this problem. So hopefully this is the first step in a broader series of studies that we can all do collectively to try to eliminate racial and ethnic disparities in cancer care and survival. Dr. Davide Soldato: So, I think that we've come at the end of this podcast. Thank you again, Dr. Lin, for joining us today. Dr. Lin: Thank you so much. It was a pleasure to be a part of this. Dr. Davide Soldato: So, we appreciate you sharing more on your JCO article, "Racial and Ethnic Disparities Along the Treatment Cascade Among Medicare Fee-for-Service Beneficiaries With Metastatic Breast, Colorectal, Lung, and Prostate Cancer." If you enjoy our show, please leave us a rating and review and be sure to come back for another episode. You can find all ASCO shows at asco.org/podcasts. 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.

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CDK4/6 Inhibitors in HR-Positive/HER2-Negative Breast Cancer: Experts Answer Your Questions

CCO Oncology Podcast

Play Episode Listen Later Aug 26, 2025 20:20

In this episode, Drs William J. Gradishar, Heather McArthur, and Joanne Mortimer address audience questions from a recent live event on the use of CDK4/6 inhibitors in patients with early and metastatic breast cancer, including:Genomic testing options for assessing risk of recurrenceAdjuvant treatment duration and holidays with CDK4/6 inhibitorsManaging renal toxicities, prophylaxis for DVT, and asymptomatic ILDCDK4/6 inhibitors with inavolisib and fulvestrantPresenters:William J. Gradishar, MD, FACP, FASCOBetsy Bramsen Professor of Breast OncologyRobert H. Lurie Comprehensive Cancer CenterNorthwestern UniversityChicago, IllinoisHeather McArthur, MD, MPH, FASCOProfessor, Department of Internal MedicineClinical Director, Breast Cancer ProgramKomen Distinguished Chair in Clinical Breast Cancer ResearchUT Southwestern Medical CenterDallas, TexasJoanne Mortimer, MD, FACP, FASCOVice Chair, Medical OncologyProfessor, Division of Medical Oncology & Experimental TherapeuticsAssociate Director for Education and TrainingBaum Family Professor of Women's CancersCity of Hope Comprehensive Cancer CenterDuarte, CaliforniaLink to full program:https://bit.ly/4osHLTm

women education positive md negative breast cancer mph diarrhea inhibitors genomic pallas her2 dvt deep vein thrombosis creatinine cdk4 nsai palbociclib oncotype

Stay Ahead of the Curve on CDK4/6 Inhibitor Toxicities

Cancer Buzz

Play Episode Listen Later Aug 7, 2025 6:37

Anticipating and managing CDK4/6 inhibitor toxicities in HR+ HER2- breast cancer is essential to improving patient quality of life and optimizing clinical outcomes. In this episode, CANCER BUZZ speaks with Diana Van Ostran, PharmD, BCOP, clinical pharmacy specialist – breast clinic at Miami Cancer Institute, Baptist Health South Florida, about strategies to monitor and manage treatment-related adverse events in patients with early-stage and metastatic breast cancer receiving CDK4/6 inhibitors. She discusses the importance of individualized care and robust patient education around lifestyle and dietary techniques to improve tolerance of this treatment. Diana Van Ostran, PharmD, BCOP Clinical Pharmacy Specialist – Breast Clinic Miami Cancer Institute Baptist Health South Florida Miami, FL “Clinical pharmacists play a vital role in managing the patient's treatment. Because, as we know, if you're having excessive side effects, patients are going to be less likely to take their medications.” Resources: ACCC Adverse Event Management for CDK Inhibitors in HR+ Breast Cancer ACCC CDK Inhibitors Management Miami Cancer Institute ACCC Spotlight on Miami Cancer Institute: The Role of a Breast Cancer Clinical Pharmacy Specialist for CDK4/6 Inhibitor Management

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Simultaneous targeting of CDK4/6 and BETs is independent of RB status in osteosarcoma

MIB Agents OsteoBites

Play Episode Listen Later Jul 25, 2025 59:37

Osteosarcoma Webinar Series: Karen E. Pollok, PhD, and Pankita H. Pandya, PhD, from the Indiana University School of Medicine, join us on OsteoBites to discuss their work exploring CDK4/6i, particularly in the context of BET inhibition, as a therapeutic option for pediatric OS, regardless of RB status.Hyperactivation of cyclin-dependent kinases 4 and 6 (CDK4/6) has been identified as an actionable molecular signature in pediatric and AYA OS patients at the Indiana University School of Medicine and others. While targeting CDK4/6 has shown promise in significantly reducing tumor progression in many cancers, resistance to CDK4/6 inhibition remains a challenge. To maximize CDK4/6 inhibitor (CDK4/6i) efficacy, a combination therapy will likely be required to mitigate emergence of resistance. Moreover, retinoblastoma proficiency (RB+) has been used as a biomarker to predict response and stratify patients for treatment with CDK4/6 inhibitors in other cancers. This is concerning in the context of OS, since over 70% of OS patients harbor a retinoblastoma deficiency (RB-). Therefore, validation of RB as a biomarker of therapeutic response to CDK4/6 inhibition in OS is needed. The lab's objective in these investigations is to identify rational drug combinations that enhance efficacy of CDK4/6 inhibition, and test prioritized combinations in both RB+ and RB- OS models. Their findings support further exploration of CDK4/6i, particularly in the context of BET inhibition, as a therapeutic option for pediatric OS, regardless of RB status.Dr. Pollok is the Associate Director of Basic Science and Director of the Preclinical Modeling and Therapeutics Shared Resource Facility for the IU Simon Comprehensive Cancer Center (IUSCCC). Dr. Pollok works with cancer research laboratories in the IUSCCC to enhance programmatic science focused on translation to the clinic. In her own lab, she leads a team-oriented research program that brings together basic scientists and clinicians focused on finding cures for aggressive cancers such as sarcomas and brain tumors. Her team utilizes multi-omics data to prioritize the testing of novel combination therapies and has developed over 60 tumor models from pediatric and adolescent patients treated at the Riley Hospital for Children IU Health. In collaboration with Dr. Pankita Pandya and the Pediatric Precision Genomics Program, they employ multi-omics data from these models to focus on testing new molecularly-guided targeted therapies. Their goal is to understand the mechanisms behind therapy-mediated tumor efficacy and emerging resistance.Dr. Pandya is heavily involved in translational team science, where she works in partnership with the Pediatric Precision Genomics Program at the Riley Hospital for Children at IU Health, as well as under the mentorship of Dr. Karen E. Pollok at the Herman B Wells Center. Her research initiatives involve testing novel targeted therapies for improving therapeutic outcomes while minimizing toxicity in pediatric and young adult solid cancers like sarcomas. As a genomics data scientist, she has training in multi-omics data management and mining. Additionally, Dr. Pandya has extensive expertise in in-vivo modeling of aggressive pediatric sarcomas. Such skillsets have enabled Dr. Pandya to identify risk signatures, biomarkers of therapeutic response, and other clinically-relevant therapeutic vulnerabilities in pediatric sarcoma patients for functional validation using molecularly characterized preclinical models that our translational team has developed.

director children phd medicine os independent status bet associate director targeting bets rb simultaneous indiana university school pandya basic science osteosarcoma iu health cdk4 riley hospital

Metastatic Breast Cancer — Proceedings from a Session Held During the 2025 ASCO Annual Meeting

Play Episode Listen Later Jul 3, 2025 117:47

Featuring perspectives from Dr Harold J Burstein, Dr Javier Cortés, Prof Rebecca A Dent, Dr Kevin Kalinsky, Dr Hope S Rugo and Dr Joyce O'Shaughnessy, moderated by Dr Rugo, including the following topics: Introduction (0:00) Optimizing the Management of HER2-Positive Metastatic Breast Cancer (mBC) — Dr Cortés (3:52) Individualized Selection of Up-Front Therapy for Patients with HR-Positive, HER2-Negative mBC — Dr Kalinsky (23:10) Available Therapies for Patients with HR-Positive, HER2-Negative Disease Progressing on CDK4/6 Inhibition — Dr Burstein (48:09) Current and Potential Future Role of HER2-Targeted Therapy for HER2-Low and HER2-Ultralow Disease — Dr O'Shaughnessy (1:04:00) Current and Future Strategies for Patients with Endocrine-Refractory HR-Positive mBC — Dr Rugo (1:22:28) Selection and Sequencing of Therapy for Patients with Metastatic Triple-Negative Breast Cancer — Prof Dent (1:42:51) CME information and select publications

management therapy current patients optimizing selection annual meetings proceedings cme sequencing metastatic breast cancer asco annual meeting cdk4 javier cort rugo hope s rugo kevin kalinsky

S13 Ep20: ASCO 2025 Plenary: SERENA-6

Play Episode Listen Later Jun 24, 2025 12:33

In this episode, OncLive On Air® partnered with Two Onc Docs to bring discussion of data from the phase 3 SERENA-6 trial (NCT04964934), which were presented at the 2025 ASCO Annual Meeting. SERENA-6 evaluated switching to camizestrant plus a CDK4/6 inhibitor vs continuing with a standard-of-care aromatase inhibitor plus a CDK4/6 inhibitor in the frontline setting in patients with hormone receptor–positive, HER2-negative advanced breast cancer whose tumors harbor an emergent ESR1 mutation. Drs Armstrong and Tawagi highlighted key efficacy, safety, and patient-reported outcomes from the study. They also noted the clinical implications of these findings, including how they might be currently applicable to clinical practice, as well as limitations of the research that warrant further investigation.

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Breast Cancer Research Poised to Change Practice From ASCO25

ASCO Daily News

Play Episode Listen Later Jun 23, 2025 31:39

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

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For Oncology Nurses: Hormone Receptor-Positive Breast Cancer — Proceedings from the 2025 Annual ONS Congress