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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.  

As targeted protein degradation gains momentum, oral selective estrogen receptor degraders are emerging as one of its most advanced proving grounds. On the latest BioCentury This Week podcast, BioCentury's Lauren Martz assesses how the oral SERD landscape is evolving.Washington Editor Steve Usdin then discusses setbacks at FDA for an orphan therapy from Disc Medicine and a vaccine from Moderna, and why he is calling on life sciences industry leaders to publicly demand the dismissal of Vinay Prasad, FDA's CSO, CMO, and director of CBER.View full story: https://www.biocentury.com/article/658455#TargetedProteinDegradation #OralSERDs #OncologyDrugDevelopment #FDASetbacks #CBER00:00 - Introduction03:12 - Oral SERD Spotlight11:40 - Setbacks at FDA15:12 - Disc Medicine CRLTo submit a question to BioCentury's editors, email the BioCentury This Week team at podcasts@biocentury.com.Reach us by sending a text

Galīsiešu režisora Olivera Lašes tuksneša odiseja "Sirāts" – viena no radikālākajām pērnā gada Eiropas filmām, transam līdzīga kino pieredze, kas meistarīgi savij ģimenes un pasaules gala tēmas. Saruna ar režisoru Oliveru Laši (Oliver Laxe) un galveno aktieri Serdži Lopesu (Sergi López) Eiropas Kino akadēmijā Berlīnē. Vai kino var kļūt par rituālu pieredzi un novest skatītāju līdz katarsei? Par to saruna ar diviem spožiem Eiropas māksliniekiem, kuru balsis šais platuma grādos daudz nav skanējušas. Divas personības, kas savās mājās komentārus neprasīja agrāk, bet līdz ar filmu „Sirāts” ir kļuvušas pazīstamas drosmīga kino mīļiem daudzviet pasaulē. Kino apskatnieki to mēdz dēvēt par vienu no pērnā gada radikālākajām filmām. Par katarses ceremoniju. Par nāves deju tuksnesī. Galīsiešu režisora Olivera Lašes filma „Sirāts” vienaldzīgu neatstāj, tomēr to skatīties – vai drīzāk just – nav viegli. Tā caururbj skatītāju ne vien ar skaudriem sižeta pavērsieniem, bet visupirms – ar pulsējošiem tehno ritmiem un elpu aizraujošiem Marokas tuksneša skatiem. Filma „Sirāts” pērn ieguva Kannu kinofestivāla Žūrijas balvu un tagad pretendē uz diviem Oskariem – par labāko ārzemju filmu un labāko skaņu. „Sirāts” saņēma arī virkni balvu Eiropas Kinoakadēmijas ceremonijā šā gada janvārī, galvenajās kategorijās gan piekāpjotie, kinokritiķes Ditas Rietumas vārdiem, „gaumīgajai mērenībai” – norvēģu filmai „Sentimentālā vērtība”. Bet „Sirāts” turpina likt par sevi runāt un no 20. februāra filmu varēs skatīties arī Latvijas kinoteātros. Slava režisoram Oliveram Lašem seko jau kopš viņa pirmās pilnmetrāžas filmas „Jūs visi esat kapteiņi”, kas 2010. gadā tika pirmizrādīta Kannu kinofestivālā un saņēma Starptautiskās Kinokritiķu federācijas (FIPRESCI) balvu. Kannās Laše ir atgriezies arī ar savām nākamajām filmām un nekad nav aizbraucis mājās tukšām rokām. Viņa ceturtā filma „Sirāts” ieguva Kannu kinofestivāla Žūrijas balvu.  Olivers Laše ir dzimis Francijā, bet viņa vecāki ir no Galīsijas. Režisors arī atgriezies uz dzīvi Galīsijā Spānijas ziemeļrietumos un arī mūsu sarunā uzsver, ka galīsiešu mantojums viņam ir ļoti svarīgs. Mēs tiekamies nelielā žurnālistu lokā īsi pirms Eiropas Kinoakadēmijas balvu pasniegšanas Berlīnē. Laše ir neparasta personība ar spēcīgu vizuālo tēlu: viņš ir divus metrus garš (savulaik nopietni trenējies basketbolā), ar gariem, tumšiem pāri mugurai viļņojošiem matiem un fotomodeļa skatienu. Viņš studē geštaltterapiju, ir mistiķis un savā domu pasaulē harizmātiski ievelk arī apkārtējos.  Kad Lašem jautā par sadarbību ar dīdžejiem filmas „Sirāt” tapšanā, 43 gadus vecais režisors rāmi atlaižas krēslā, un ir sajūta, ka interviju telpā ienāk kaut kas no reiva noskaņas. „Pirmkārt, jums jāsaprot, ka es filmas kadrus vispirms izdejoju. Es pats devos uz reiviem tuksnesī. Starp citu, pats piecus gadus dzīvoju Marokā. Un filmas scenārijs pamazām tapa manā galvā, kamēr es dejoju,” sarunu uzsāk Olivers Laše. „Arī reālais scenārija rakstīšanas process ir ļoti atmosfērisks. Un mūzika ir atmosfēra. Domāju, ka mans jūtīgums kā māksliniekam ir ļoti saistīts ar skaņu, ar šo slāņaino attēla un skaņas struktūru. Manos scenārijos vienmēr ir saites uz mūziku. Šajā filmā es negribēju strādāt ar komponistu, bet gan ar aktīvu mūziķi. Veicu atlasi, un Kangdings Rejs (Kangding Ray) izrādījās labākais. Man vajadzēja kādu, kurš spēj veidot dialogu ar šo katartisko tehno mūziku, kas ir cieši saistīta ar tautas mūziku, bet kurš vienlaikus spētu radīt arī ēteriskāku, ambientāku mūziku.”     Par savu gada filmu „Sirātu” nosauca arī kino kritiķe Dārta Ceriņa, kad mūsu raidījumā „Kur kritiķiem nav vietas” kopsavilka pērnā gada kino ražu.

Oficiālā atklāšanas ceremonija vēl tikai šovakar, bet ziemas olimpiskās spēles Itālijā jau ir sākušās. Trešdien un ceturtdien kalnu slēpotāji, kērlinga meistari, snovbordisti un hokejistes sāka savus startus. Pulksten 21:00 sāksies spēļu atklāšanas ceremonija. Tiešraidē to, protams, raidīs arī Latvijas TV. Gaidot atklāšanas ceremoniju, uzklausām, ko no tās cer sagaidīt mūsu delegācija. Stāsta Harijs Vitoliņš, Latvijas hokeja izlases galvenais treneris un karognesējs 2002. gadā, kā arī olimpisko spēļu debitants, hokejists Kristiāns Rubīns. Sazināmies arī ar Jāni Ķipuru, kurš bija karognesējs 1992. gadā Albervilā, Francijā. Kopā atmināmies to laiku un iezīmējam arī to, kas gaidāms šajās spēlēs. Spēļu atkāšanas ceremonija notiks leģendārajā San Siro stadionā Milānā, kur ikdienā spēlē futbolu, un tas ir viens no leģendārākajiem futbola stadioniem pasaulē. Lai gan nekas vēl nav oficiāli paziņots, gaidāms, ka atklāšanas ceremonija savā ziņā būs arī veltījums stadiona vēsture. Stadionā ir vietas aptuveni 80 tūkstošiem līdzjutēju, un tas tika atvērts tieši pirms 100 gadiem. 2025. gada rudenī Milānas pilsēta nobalsoja par stadiona nojaukšanu, un tā vietā pēc kāda laika sliesies jauns stadions. Kā to nosaka Olimpiskā harta, pasākuma programmā būs mākslinieciskie priekšnesumi, kas atspoguļos rīkotājvalsts, tātad Itālijas, un rīkotājpilsētu – Milānas un Kortīnas – kultūru, būs sportistu parāde un olimpiskās uguns iedegšana. Spēles oficiāli atklās Itālijas prezidents Serdžo Matarella. Šīs būs pirmās ziemas olimpiskās spēles, kuru atklāšanas ceremonija notiks Starptautiskās Olimpiskās komitejas prezidentes Kērsijas Koventrijas prezidentūras laikā.  Atklāšanas ceremonijas scenārijs, kā allaž, tiek turēts noslēpumā, bet naskākie mediju izlūki pasaulē ir snieguši savus minējumus. Pastāv uzskats, ka mūzika būs ceremonijas centrālais elements, lai gan līdz šim ir apstiprināti tikai daži mākslinieki. Ceremonijas koncepcija paredzot izcelt vairākas sacensību norises vietas. 25. ziemas olimpiskajās spēlēs kopumā plāno startēt 2871 sportists un sportiste no 92 valstīm, bet Latviju pārstāvēs 68 sportisti. Šī ir lielākā delegācija, ar kādu Latvija jebkad piedalījusies ziemas spēlēs. Mums būs atlēti biatlonā, bobslejā, kamaniņās, skeletonā, daiļslidošanā, distanču slēpošanā, kalnu slēpošanā, šorttrekā un, protams, arī hokejā - mūsu vīru hokeja valstsvienība 7. reizi piedalīsies olimpiskajās spēlēs, ja ieskaitām arī vienu reizi pirms padomju okupācijas laika.  Tieši hokeja izlases kapteinis, Triju zvaigžņu ordeņa kavalieris Kaspars Daugaviņš būs viens no mūsu karognesējiem atklāšanas ceremonijā. Viņš to darīs līdzās mūsu kalnu slēpotājai Dženiferai Ģērmanei.  Hokejisti visbiežāk nesuši mūsu karogu - sākot ar Leonīdu Jāni Vedēju 1936. gadā Bavārijā, bet pēc neatkarības atgūšanas to darījuši vīri, kuri tagad jau ir izlases treneru štābā - Harijs Vītoliņš, Artūrs Irbe, Sandis Ozoliņš un Lauris Dārziņš. Gandrīz tikpat bieži arī bobslejisti bijuši mūsu karognesēji. Mūsu sportistiem pirmie starti rītdien, 7. februārī. Rīta pusē Elvis Opmanis aizvadīs nobraucienu kalnu slēpošanā, vēlāk skiatlonā sacensības sāks mūsu slēpotājas Patrīcija Eiduka, Kitija Auziņa, Linda Kaparkalēja un Samanta Krampe, bet vakarpusē pirmie divi braucieni mūsu kamaniņiekiem Kristeram Aparjodam un Gintam Bērziņam.  Precīzāka informācija par starta laikiem meklējama portālā lsm.lv un pašas sacensības varat skatīties kanālā LTV7.

Did you know that as MBC patients get treated with multiple lines of ET, the percentage of patients who develop an ESR1 mutation increases? Credit available for this activity expires: 1/26/27 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/current-and-future-oral-serd-strategies-management-er-2026a100022b?ecd=bdc_podcast_libsyn_mscpedu

Eiropas Kinoakadēmija nosaukusi Eiropas kino industrijas izcilības. Balvu pasniegšanā klāt bija arī Latvijas Sabiedriskais medijs, sekojot līdzi mūsu „Dieva suņa” gaitām, kas bija nominēts animācijas filmu kategorijā. Lai gan filma balvu šoreiz neieguva, starptautiskajai kino pasaulei spoži apliecināja, cik dažāda animācijas valoda var nākt arī no tik nelielas valsts kā Latvija. ““Dieva suns” ir “smagais metāls”. Rotoskopēta animācijas filma, kuras darbība risinās 17. gadsimta Baltijā, par raganu medībām, vilkati un sātana pautiem. Murgs, kuru nespēsiet aizmirst,”  tik krāšņi animācijas pieciniekā Eiropas Kinoakadēmijas balvu ceremonijā tika pieteikta brāļu Ābeļu filma, nešaubīgi izceļoties uz ierastā bērnu un ģimenes animācijas fona. Balvu animācijas filmu kategorijā ieguva franču zinātniskās fantastikas filma bērniem „Arco”. Kad svētdienas rītā tiekamies ar “Dieva suņa” komandu – režisoriem Lauri un Raiti Ābelēm, mākslinieku Hariju Grundmani un scenāristu Ivo Briedi – viņu noskaņojums ir neviltoti pacilāts, un par neiegūto balvu viņi daudz nebēdā. Lielāki par balvu ir citi ieguvumi. Brāļi smejas, ka ballītē pēc ceremonijas sadraudzējušies ar slaveno katalāņu aktieri Serdži Lopezu (Sergi López), kurš bija nominēts par lomu filmā “Sirāts”, un aicināšot viņu spēlēt savā nākamajā filmā “Vāgners un Sātans”. Scenārists Ivo Briedis saticis un pie saviem studentiem uz Rīgu uzaicinājis britu avangarda klasiķi Džonu Smitu. Vārdu sakot, “Dieva suņa” starptautiskā parāde atvērusi durvis personiskiem kontaktiem, saka Lauris Ābele. Tas viņam ir svarīgākais. Raitis Ābele piekrīt. Eiropas Kinoakadēmijas balvai šogad esot tikuši izskatīti 42 animācijas filmu pieteikumi, tātad izredzes tikt nominantu pieciniekā bija vairāk nekā viens pret astoņi. ASV strādājošais filmas itāļu producents ar skanīgo vārdu Džovanni Labadesa (Giovanni Labadessa) “Dieva suņa” iekļūšanu starp nominantiem vērtē kā veselīgu attieksmi pret Eiropas kino daudzveidību.  

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

In this episode of The Oncology Brothers, we were joined by Dr. Laura Huppert from UCLA to discuss the latest practice-changing findings from the SABCS 2025 conference, focusing on early-stage hormone receptor-positive breast cancer. Join us as we dive into three key abstracts: 1. ALTTO Study: Discover the results comparing aromatase inhibitors to tamoxifen in triple-positive breast cancer and the implications for treatment strategies. 2. lidERA Study: Learn about the promising data on the oral selective estrogen receptor degrader (SERD) giredestrant, which shows significant improvement in invasive disease-free survival compared to standard endocrine therapy. 3. NATALEE Trial: Get insights into the five-year update on ribociclib in combination with aromatase inhibitors, highlighting its benefits across different patient subgroups (stages, nodal status). We explored the evolving landscape of endocrine therapy, the importance of side effect profiles, and how these findings may influence clinical practice moving forward. Don't miss this informative discussion that could reshape your approach to treating early-stage hormone receptor-positive breast cancer! Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Subscribe to our channel for more updates on treatment algorithms, recent approvals, and conference highlights. #SABCS2025 #BreastCancer #AdjuvantTherapy #Giredestrant #Ribociclib #AI #OncologyBrothers #HRpositiveBC

The 2025 San Antonio Breast Cancer Symposium featured four days filled with new research findings, poster presentations, and educational sessions. Marisa Weiss, MD, founder and chief medical officer of Breastcancer.org, offers her take on the top results. Listen to the episode to hear Dr. Weiss explain: how giredestrant, a new oral SERD for early-stage, hormone receptor-positive breast cancer, may change practice a new use for Tukysa (chemical name: tucatinib) in metastatic HER2-positive disease the lifestyle factors that can affect breast cancer risk and steps people can take to keep their risk as low as possible

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

El Dr. Mauricio Lema, hemato-oncólogo adscrito a la Clínica de Oncología Astorga en Medellín, Colombia, presentó una actualización integral sobre los avances más relevantes en oncología para 2025, con énfasis en cáncer de mama y cáncer de pulmón. Su intervención destacó los resultados de los estudios DESTINY-Breast09, DESTINY-Breast05 y DESTINY-Breast11 en enfermedad HER2 positiva, así como los avances en enfermedad luminal con biomarcación por ESR1 y el papel emergente de camizestrant y nuevos SERD. En cáncer de pulmón de células no pequeñas, subrayó la madurez del CheckMate 816 con beneficio claro en supervivencia global a 5 años, además de los resultados de supervivencia global de los estudios FLAURA2 y MARIPOSA en EGFR mutado, y el impacto de nuevas terapias dirigidas como sacituzumab tiromutecán, cefavertinib y zongertinib. Finalmente, abordó la revolución terapéutica en cáncer de pulmón de células pequeñas con el estudio DeLLphi-304 y el uso de tarlatamab, así como datos preliminares del estudio IMforte. Su intervención se llevó a cabo durante el 9° Congreso Nacional de Actualización en Hematología y Oncología de la ACHO, realizado del 14 al 16 de noviembre de 2025 en Cartagena de Indias, Colombia.Fecha de grabación: 15 de noviembre de 2025Referencia:Este contenido se basa en la interpretación crítica de la evidencia científica disponible, así como en la experiencia clínica del o los ponentes como profesionales de la salud en instituciones de referencia.Para profundizar en los conceptos discutidos, se recomienda al profesional de la salud consultar literatura científica vigente, guías clínicas internacionales y la normatividad aplicable en su país.

Why is Ukraine plastered across Hungary's billboards and campaign ads as if it were on the ballot itself? And what does Viktor Orbán really gain from keeping Volodymyr Zelensky in the minds, hearts and social media algorithms of Hungarians?In this episode of the Visegrad Insight Podcast, Wojciech Przybylski speaks with Viktória Serdült, journalist at HVG in Budapest, about how Ukraine became the central prop of Hungary's permanent election campaign.Together they discuss:How the ‘pro-war / pro-peace' propaganda line turned into a full-blown anti-Ukraine campaign in HungaryWhy Zelensky, Ursula von der Leyen and Péter Magyar are glued together on Fidesz billboards as the alleged ‘pro-war' trioWhat ordinary Hungarians actually think about the war and Ukraine's EU membership, beyond government messagingThe role of the Hungarian minority in Ukraine and long-term mistrust in shaping public opinionHow agriculture, gas transit and EU funds quietly sit behind the slogans about peace and sovereigntyWhy Russia is barely mentioned in Budapest's rhetoric about a war that Moscow startedWhat to watch in 2025–2026 as Hungary heads into yet another high-stakes electoral cycle with Ukraine at the centreWatch on YouTube: https://youtu.be/jdmBOuqQgLwListen on Spotify: https://open.spotify.com/episode/6DjmhfAz6U2y4zOqa9zQ5u?si=z-nh1ZYNQj6dtGUp1V3Kbg

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

Ce soir, c'est Rania à l'animation ! En première partie, Vladimir reçoit Chloé Liboureau, Présidente de Réseau étudiant pour une société écologique & solidaire (RESES), au sujet de la Semaine étudiante de la réduction des déchets (SERD) et de ses enjeux. Adèle est au flash info.  Céline interviewe Arnaud Dudek, auteur de romans sur la santé mentale des jeunes sportifs et le harcèlement scolaire, à propos de l'événement : "Santé mentale et intime des jeunes : et si on en parlait autrement ?" qui se tiendra le 27 novembre à la Maison de la Conversation. Félix, dans sa chronique, nous parle du plan de paix pour l'Ukraine et des récentes déclarations du Général Mando. Enfin, Eloane nous fera une chronique libre. Animation : Rania // Interview : Vladimir // Zoom : Céline // Réalisation : Joey // Flash info : Adèle // Chronique : Félix // Chronique : Eloane // Coordination : Aude & Jeanne

Ce soir, c'est Rania à l'animation ! En première partie, Vladimir reçoit Chloé Liboureau, Présidente de Réseau étudiant pour une société écologique & solidaire (RESES), au sujet de la Semaine étudiante de la réduction des déchets (SERD) et de ses enjeux. Adèle est au flash info.  Céline interviewe Arnaud Dudek, auteur de romans sur la santé mentale des jeunes sportifs et le harcèlement scolaire, à propos de l'événement : "Santé mentale et intime des jeunes : et si on en parlait autrement ?" qui se tiendra le 27 novembre à la Maison de la Conversation. Félix, dans sa chronique, nous parle du plan de paix pour l'Ukraine et des récentes déclarations du Général Mando. Enfin, Eloane nous fera une chronique libre. Animation : Rania // Interview : Vladimir // Zoom : Céline // Réalisation : Joey // Flash info : Adèle // Chronique : Félix // Chronique : Eloane // Coordination : Aude & Jeanne

C'est la Semaine européenne de la réduction des déchets (SERD), du 22 au 30 novembre 2025 ♻️Qu'on se le dise le plastique n'a plus rien de fantastique,Nous en jetterions 22 millions de tonnes chaque année dans l'environnement. Chaque minute, 15 tonnes finit dans nos océansEt l'une des solutions se trouve, figurez-vous, dans nos rayons.Réutiliser au lieu de jeter, une idée qui fait son chemin, notamment grâce à mon invitée :Célia RennessonDepuis 8 ans, Célia accompagne le secteur du 0 déchet pour les aider à développer une autre façon de consommerAlors, comment limiter l'usage des emballages ? Et pourquoi adopter le réemploi ?Voici la recette de Célia Rennesson.

Send us a textGood morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into the dynamic landscape of the industry, exploring significant scientific advancements, regulatory changes, clinical trial outcomes, and strategic investments that are shaping the future of healthcare.Starting with strategic investments, Regeneron is making a bold move with a $2 billion investment to transform a former magazine factory in Saratoga Springs, New York, into a state-of-the-art drug manufacturing plant. This investment reflects a broader industry trend towards enhancing domestic manufacturing capabilities to ensure supply chain resilience. Similarly, CSL is channeling $1.5 billion into U.S. plasma-based manufacturing over the next five years. These investments are critical as plasma-derived therapies continue to play a vital role in treating various conditions, necessitating robust manufacturing infrastructure to meet growing demand.In clinical research, Merck's Winrevair has shown promising results in a proof-of-concept study for heart failure patients. This advancement highlights ongoing efforts to address one of the leading causes of morbidity and mortality worldwide—heart failure. The study paves the way for further exploration of activin signaling inhibitors in cardiovascular therapies.On the regulatory front, Eli Lilly has expanded its market reach with the approval of its Alzheimer's medication for distribution in India. This milestone represents progress in tackling the global Alzheimer's disease burden, an ailment that presents significant challenges to healthcare systems worldwide.The FDA's recent critique of AstraZeneca's Farxiga advertisement underscores the importance of accuracy in pharmaceutical marketing. The agency's concerns about potential misleading impressions emphasize ongoing regulatory vigilance to align marketing practices with approved therapeutic uses and ensure patient safety.Shifting to business strategies, Zymeworks' transition towards becoming a 'royalty-driven organization' marks an evolution in biotech business models. By leveraging successful licensing frameworks, Zymeworks aims to enhance revenue streams while focusing on innovation without the traditional constraints of direct commercialization.In cardiovascular therapeutics, Cytokinetics is positioning itself strategically by funding a heart registry, signaling an intensifying competitive landscape as companies vie for leadership in this critical area of healthcare.Roche's development of giredestrant, an oral selective estrogen receptor degrader (SERD), has achieved success in a phase 3 adjuvant breast cancer trial. This positions Roche to capture an unoccupied niche within the competitive breast cancer treatment market and highlights a trend towards targeted therapies with potentially significant patient outcomes.Addressing side effects associated with GLP-1 receptor agonists, Vanda Pharmaceuticals is making strides with tradipitant to mitigate nausea and vomiting induced by Wegovy. As GLP-1 agonists gain traction for their metabolic benefits, adjunct therapies addressing side effects are becoming increasingly pertinent.In digital health initiatives, Humana's collaboration with Epic aims to automate insurance verification and patient check-ins, aligning with federal interoperability goals. This represents a broader industry shift towards digital solutions designed to streamline administrative processes and enhance patient experience.Meanwhile, Lonza's expansion at its Stein facility in Switzerland underscores ongoing capacity-building efforts among contract development and manufacturing organizations (CDMOs). Such expansions are crucial as they provide biopharmaceutical companies with the neSupport the show

La sonda Voyager 1 sigue viajando por el espacio: ya salió del Sistema Solar y está a una distancia de 1 día luz. Y como todos hablan de la versión de Frankenstein de Guillermo del Toro, recordamos a Mary Shelley y versiones muy mexicanas de aquella creatura. ¿Y por qué Aquiles Serdán se puso vestido? Además les hablo del mítico tornaviaje, el cual cambió el mundo para siempre. Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

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

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

Is your patient progressing on an aromatase inhibitor (AI)? Fine-tune ddPCR/NGS testing to detect resistance and optimize oral selective estrogen receptor degrader (SERD) success. Credit available for this activity expires: 11/04/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/esr1-mutation-testing-breast-cancer-setting-standard-2025a1000u0f?ecd=bdc_podcast_libsyn_mscpedu

San Lucas 14, 15 – 24Al oír estas palabras, uno de los invitados le dijo: «¡Feliz el que se siente a la mesa en el Reino de Dios!». Jesús le respondió: «Un hombre preparó un gran banquete y convidó a mucha gente. A la hora de cenar, mandó a su sirviente que dijera a los invitados: ‘Vengan, todo está preparado'. Pero todos, sin excepción, empezaron a excusarse. El primero le dijo: ‘Acabo de comprar un campo y tengo que ir a verlo. Te ruego me disculpes'. El segundo dijo: ‘He comprado cinco yuntas de bueyes y voy a probarlos. Te ruego me disculpes'. Y un tercero respondió: ‘Acabo de casarme y por esa razón no puedo ir'.A su regreso, el sirviente contó todo esto al dueño de casa, y este, irritado, le dijo: ‘Recorre en seguida las plazas y las calles de la ciudad, y trae aquí a los pobres, a los lisiados, a los ciegos y a los paralíticos‘. Volvió el sirviente y dijo: ‘Señor, tus órdenes se han cumplido y aún sobra lugar'. El señor le respondió: ‘Ve a los caminos y a lo largo de los cercos, e insiste a la gente para que entre, de manera que se llene mi casa. Porque les aseguro que ninguno de los que antes fueron invitados ha de probar mi cena'».…………….Spotify: https://open.spotify.com/show/2M0Ubx3Jh55B6W3b20c3GOApple podcast: https://podcasts.apple.com/us/podcast/evangelio-del-d%C3%ADa/id1590423907 Para más información puede consultar nuestro sitio: https://www.vozcatolica.com o escríbanos a info@vozcatolica.com .Si quiere colaborar con este Apostolado lo puede hacer dirigiéndose a: https://vozcatolica.com/ayudanos . Desde ya muchas gracias

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

Elvitelre – a podcast, amelyben a hét legjobb HVG hetilapos és hvg360-as anyagaiból válogatunk. Csak indítsa el a háttérben és hallgassa meg szerzőink legjobb írásait. A héten: Serdült Viktória: 51 perc ügyfélérdek, valamint Parászka Boróka: Akciós Békemenetjegyek című írásait hallhatjátok. 00:00 Intro 00:16 Serdült Viktória: 51 perc ügyfélérdek 08:45 Parászka Boróka: Akciós Békemenetjegyek 17:14 Outro ▶️Youtube-nézőinknek hvg360-kedvezmény:

Elvitelre – a podcast, amelyben a hét legjobb HVG hetilapos és hvg360-as anyagaiból válogatunk. Csak indítsa el a háttérben és hallgassa meg szerzőink legjobb írásait A héten: Szabó Yvette és Serdült Viktória: Magas színvonalú életvitelének biztosítására hozott létre alapítványt Szalay-Bobrovniczky Kristóf és Lengyel Tibor: Körkörös támadás című írásait olvassa fel Imre Réka. Iratkozz fel a hvg360-ra! hvg.hu/360/elofizetes ▶️Youtube-nézőinknek hvg360-kedvezmény:

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Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Genmab has acquired Merus, a rising star in the field of oncology, for $8 billion. The acquisition includes Merus' bispecific antibody, petosemtamab, which targets EGFR and LGR5 and has shown potential for head-and-neck cancer. In other news, GSK CEO Emma Walmsley is stepping down after nine years, with Chief Commercial Officer Luke Miels set to replace her next year. The FDA's decision to disclose complete response letters in real-time has raised questions about transparency and the agency's role. Additionally, Biogen has shuffled staff after ending work on AAV, while Heidelberg has cut 75% of its staff after missed royalty payments.The FDA's real-time disclosure of complete response letters benefits investors by providing greater visibility into regulatory decisions. In September, the FDA's actions included boosting Keytruda while rejecting two spinal muscular atrophy therapies due to manufacturing issues. A judge's ruling on the FDA's authority over laboratory-developed tests reflects the impact of a recent Supreme Court decision. Six FDA decisions to watch for in Q4 could have significant implications for the biopharma industry and patients. Recent developments include positive results for an immuneering asset in pancreatic cancer, FDA approval for Lilly's oral SERD for breast cancer, and positive outcomes for uniQure's Huntington's therapy. Additionally, the FDA is streamlining development of cell, gene, and regenerative therapies. Other news includes the revival of a dormant drug as a potential autism treatment, setbacks in obesity studies, and unexpected rejections for certain therapies. Upcoming webinars and job opportunities are also highlighted.Listeners are encouraged to provide feedback on topics they would like to see covered in future episodes.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.President Trump has announced a 100% tariff deadline for pharmaceutical companies starting on October 1. However, companies that have already begun construction on manufacturing facilities in the U.S. are exempt from these tariffs. This move is part of the administration's efforts to lower drug prices and improve access to treatments for patients.In other news, Crinetics Pharmaceuticals has received FDA approval for their once-daily treatment for acromegaly, a rare pituitary condition. This approval marks a significant milestone for Crinetics and is expected to have a positive impact on patients' lives.Additionally, Lilly's oral SERD has been approved by the FDA for the treatment of breast cancer. This treatment has shown improved progression-free survival compared to standard therapy, offering new hope for patients battling this disease.The Trump administration is also preparing a proposed rule to further lower drug prices in the U.S., as part of an ongoing effort to align drug prices with other economically similar countries. These developments in the pharmaceutical industry are aimed at improving access to treatments and lowering costs for patients.

Sheinbaum informó que se solicitó integrar un nuevo grupo de expertos internacionales para el caso AyotzinapaOperativos contra venta de calzado asiático arrancarán en San Mateo AtencoEn América las mujeres indígenas tienen hasta tres veces más riesgo de morir durante el partoMás información en nuestro podcast

Elvitelre – a podcast, amelyben a hét legjobb HVG hetilapos és hvg360-as anyagaiból válogatunk. Csak indítsa el a háttérben és hallgassa meg szerzőink legjobb írásait! A héten: Putyin győzelmi kényszere Ukrajnában és váratlan kormányzati gesztus a magyar nők felé. Olvass még több prémium tartalmat a hvg360-on!

En la calle Serdán de Hermosillo se levanta un edificio común, pero sus paredes guardan uno de los secretos más oscuros de la ciudad. Allí existió un convento de monjas que, lejos de ser un refugio, se convirtió en un infierno para mujeres embarazadas y sus hijos. Restos emparedados, túneles ocultos y apariciones espectrales mantienen viva la leyenda. Quienes pasan de noche aseguran escuchar llantos de bebés y ver a mujeres embarazadas flotando en el aire… almas condenadas que jamás encontraron descanso.

En la Sierra Norte de Puebla, comunidades totonacas y más activistas ambientales se unieron para frenar la construcción de presas hidroeléctricas y minería a cielo abierto que amenazaban su territorio. A través de testimonios se evidencian los impactos ambientales, sociales y en la salud, especialmente de las mujeres, mostrándonos la importancia de la organización comunitaria para proteger el agua, la tierra y el futuro y la vida. Esta es una producción de Radio Itzahuatalix con el apoyo de Cultural Survival. Nuestros programas son gratuitos para escuchar, descargar y difundir. Música de introducción: - Burn Your Village to the Ground” by The Halluci Nation. Derechos de autor, propiedad de The Halluci Nation. Usada bajo su permiso. Música de fondo: - Bajo responsabilidad de Radio Itzahuatalix Voz: - Bajo dirección de Radio Itzahuatalix Guión, producción y edición: - Radio Itzahuatalix Imagen: - Radio Itzahuatalix

En la Sierra Norte de Puebla, comunidades totonacas y más activistas ambientales se unieron para frenar la construcción de presas hidroeléctricas y minería a cielo abierto que amenazaban su territorio. A través de testimonios se evidencian los impactos ambientales, sociales y en la salud, especialmente de las mujeres, mostrándonos la importancia de la organización comunitaria para proteger el agua, la tierra y el futuro y la vida. Esta es una producción de Radio Itzahuatalix con el apoyo de Cultural Survival. Nuestros programas son gratuitos para escuchar, descargar y difundir. Música de introducción: - Burn Your Village to the Ground” by The Halluci Nation. Derechos de autor, propiedad de The Halluci Nation. Usada bajo su permiso. Música de fondo: - Bajo responsabilidad de Radio Itzahuatalix Voz: - Bajo dirección de Radio Itzahuatalix Guión, producción y edición: - Radio Itzahuatalix Imagen: - Radio Itzahuatalix

Elvitelre – a podcast, amelyben a hét legjobb HVG hetilapos és hvg360-as anyagaiból válogatunk. Csak indítsa el a háttérben és hallgassa meg szerzőink legjobb írásait! A héten: kórházi klímakrízis és kuruzslásveszély. Iratkozz fel a hvg360-ra! hvg.hu/360/elofizetes Az e heti menü: 00:16 Átmeneti fellángolás volt a tavalyi válságkezelés, befagyott a kórházi klímaprogram (Galicza Dorina, Fetter Dóra) 08:29 Szépségipari balesetek (Serdült Viktória)

Hoy reconocemos que nuestras acciones del presente son las que nos guían a construir nuestro futuro.–A lo largo de estos 4 años de Despertando Podcast, hemos compartido episodios que les han ayudado muchísimo, y hoy queremos traerles de vuelta todas esas herramientas que han resonado con ustedes y cambiado sus mañanas ☀️.En este episodio hablamos de:Reconocer todo eso que has logrado hasta este momentoHacernos responsables de nuestro presente y nuestro futuroDarnos permiso de soñar y construir el camino que nos lleve a hacerlo posibleSi quieres conocer más de Despertando Podcast síguenos en nuestras redes sociales:

¿Qué perderías por una idea?La casa de los Hermanos Serdán en Puebla se convirtió en la primera trinchera real de la Revolución Mexicana dando el verdadero inicio el 18 de noviembre y no el 20 de noviembre como nos hicieron creer para olvidarlos. En este episodio nos acompañó nuestra amiga Ana Corcuera para platicar sobre cómo es que entre panfletos escondidos y rifles contrabandeados, Carmen, Aquiles, Natalia y Máximo desafiaron al régimen de Porfirio Díaz dos días antes del 20 de noviembre. Descubre cómo su comedor se volvió cuartel, por qué el disparo que mató a Aquiles sacudió al país y cómo el Estado olvidó a quienes iniciaron la lucha que cambió México.

Elvitelre – a podcast, amelyben a hét legjobb HVG hetilapos és hvg360-as anyagaiból válogatunk. Csak indítsa el a háttérben és hallgassa meg szerzőink legjobb írásait! A héten: Orbán nemzetközi befolyása, és a gyermekotthonok helyzete. Iratkozz fel a hvg360-ra! hvg.hu/360/elofizetes Az e heti menü: Serdült Viktória interjúja Hegedűs Dániellel Szabó Yvette: Pokoli gyermekotthonok Olvass még több prémium tartalmat a hvg360-on! Próbáld ki a hvg360-at most féláron

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  

You've probably heard that authoritarianism is on the rise across the globe. Increasingly, countries are adopting policies that undermine democracy, reduce accountability, and erode civil liberties and human rights. But why is authoritarianism on the rise, and how do authoritarian leaders come to power? Lauded by Donald Trump and condemned by rights-defenders, Hungary's Prime Minister Viktor Orban provides a useful case study for those hoping to better understand the authoritarians' playbook. This week, host Ngofeen Mputubwele speaks to a Hungarian journalist and civil liberties strategist to map Orban's journey to autocracy, and how his lurch towards authoritarianism has decimated civil liberties and allowed him to exert a stranglehold on Hungarian politics for more than 15 years. Stefania Kopronczay: Former director of the Hungarian Civil Liberties Union; visiting scholar at Columbia University Viktória Serdült: Journalist at HVG.HU

Llegamos al noveno paso en este camino llamado Historia y Teología de la Reforma Radical. En este episodio, el maestro Fabián Cabezas, especialmente aborda el testimonio de las iglesias anabautistas como discípulas del Señor en medio de un contexto de persecución y de sismos sociales. Un Momento de Anabautismo se ha ido al podcast Textos IBA y traemos esta bella serie que nos cuenta sobre las bases históricas, comunales y teológicas de las iglesias Anabautistas.

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

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

Elvitelre – a podcast, amelyben a hét legjobb HVG hetilapos és hvg360-as anyagaiból válogatunk. Csak indítsa el a háttérben és hallgassa meg szerzőink legjobb írásait! A héten: üldözési törvényjavaslat Magyarországon. Iratkozz fel a hvg360-ra! hvg.hu/360/elofizetes A mai menü: 00:00 Intro 00:16 Elmagyarázzuk, mivel jár és mi a legveszélyesebb a Fidesz új üldözési törvényében – kérdések, válaszok és kétségek (Serdült Viktória, Lengyel Tibor)

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

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

Catch up on new data from San Antonio on innovative treatments and patient-centered management strategies for estrogen receptor (ER)-positive metastatic breast cancer (MBC). Credit available for this activity expires: 01/13/26 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1002163?ecd=bdc_podcast_libsyn_mscpedu

Somos dóciles al Espíritu Santo haciendo nuestro cuerpo grato a Él, al pedirle que nos afiance en los misterios de la fe y al orar junto a María, los santos, el ángel de la guarda y en comunidad.

* El debate sobre cómo se cocina el fentanilo * Año empieza con impuesto a comercio electrónico * Y no puede ser Día de Reyes sin la rosca del Costco

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