Podcasts about Dato

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  

Il Messaggio di Oggi: “CHIEDETE E VI SARÀ DATO” • Matteo 7: 7 • Matteo 21 :22 • Giacomo 5 :16 • Matteo 6: 9-10 • Marco 6: 25 • Luca 11: 11-12 • Romani 8 :9 • Romani 8: 13 • 1 Giovanni 4 :4-6 • Matteo 26: 41 • 1 Pietro 1: 24 • Romani 7: 24-25 • Colossesi 3 :2 • Romani 7: 15 • Luca 11: 12-13 • 1 Corinzi 14: 1 • Colossesi 3: 1 • Efesini 5: 18--Guarda Canale 245 | Tivùsat 454 | Sky 854Scopri di più su www.paroledivita.org/linkinbio

Es útil básicamente para cuando solicitas sobreseimiento. También en revisión de medida cautelar. Es aquel dato que no tomó en cuenta el Juez de control al no existir en ese momento en la carpeta o que se desconocía.

Comentario de actualidad del periodista Andreu Manresa

En este episodio nos metemos de lleno en la variabilidad de la frecuencia cardíaca (HRV) y en cómo puede ayudar (y también confundir) a los corredores de fondo. Vamos a analizar cómo interpretar las subidas y bajadas del HRV, cuándo pueden ser una señal de fatiga, estrés o falta de recuperación y cuándo simplemente son ruido normal del organismo, incluyendo factores como el sueño, el invierno, el alcohol o los cambios de rutina. Y lo mas importante cómo utilizar tú mismo el HRV para ajustar tus semanas de carga, decidir cuándo apretar y cuándo levantar el pie, y cómo puede ser una referencia muy útil para gestionar la recuperación después de una maratón o un ultra, siempre entendiendo sus límites y evitando obsesionarse con un solo número.​Cada pedido con un importe superior a 35€ recibirá un producto sorpresa de los nuevos lanzamientos.CUPÓN: MBPC

Maracanà con Marco Piccari e Stefano Impallomeni. Ospiti: Cugini:"Segnale forte da Neres. ADL simpatico e intelligente. Paganini:"I grandi colpi di ADL Kvra e Osimhen comprese le cessioni" Gaito:"Il Napoli ha dato una grande risposta per il campionato" Impallomeni:" Conte ha ridato sprint al Napoli

Når et menneske synder har det en pris og noen må betale. Problemet er at vi mennesker legger kostnaden på andre. I julefortellingen ser vi historien om en som kom for å leve motsatt. En som gav seg selv for å betale for andres synd. I denne talen får du høre hvordan disse gode nyhetene gjør noe med hvordan vi lever. Bibeltekst: Matt 2.13-18, Jer 31.15, Matt 20.28, 2. Kor 5.21,  Dato: 21. desember 2025 Taler: Magnus Nebdal Tid: 37 min

Escuche esta y más noticias de LA PATRIA Radio de lunes a viernes por los 1540 AM de Radio Cóndor en Manizales y en www.lapatria.com, encuentre videos de las transmisiones en nuestro Facebook Live: www.facebook.com/lapatria.manizales/videos

Comentario de actualidad del periodista Andreu Manresa

‘Repasamos las contraseñas más usadas en España y en el mundo en 2025 y por qué siguen siendo "un regalo" para el cibercrimen al no superar ninguna barrera de seguridad. Anotamos consejos para que sean eficientes y recordables y descubrimos las tecnologías que cambiarán las contraseñas en un futuro no tan lejano.

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16/12 Risk off da Wall Street all'Asia. Futures a Wall Street in rosso, Nasdaq sotto pressione. Prese di profitto sull'oro, Bitcoin stabile. Oracle e Broadcom ancora in calo nel pre-market, CDS Oracle sui massimi dal 2009. Oggi il dato sul mercato del lavoro di novembre e le vendite al dettaglio. Stephen Miran, FED: tassi inutilmente restrittivi colpiscono mercato del lavoro. Casa Bianca, resistenze su candidatura Hassett. Il Nasdaq punta alle negoziazioni ai supplementari dalla seconda metà del 2026. Kospi e Nikkei sono i peggiori, attesa per BOJ e dichiarazioni Ueda. Anche l'europa in rosso, oggi il pacchetto automotive della Commissione. Manovra, spuntano interventi per 3,5 miliardi. Titoli: Caltagirone, Juventus, Unicredit.  Learn more about your ad choices. Visit megaphone.fm/adchoices

Tag med på en tidsrejse gennem Bibelens store fortælling – fra Abraham til Betlehem – og oplev, hvordan Guds løfter holder, selv når ventetiden er lang. I denne familiegudstjeneste fejrede vi advent med: ✅ Luciaoptog – lys i mørket ✅ Spirekor – sang og glæde ✅ Prædiken ved Jóannis Fonsdal og Maria, der fortæller om Guds geniale plan, som begyndte for tusinder af år siden og blev opfyldt i Jesus. ✅ Evangelielæsning fra Lukas 1,67-80 Budskabet er klart: Gud holder sine løfter. Verdens største gave er Jesus – lyset, der skinner i mørket og bringer håb og fred.

Episod 182 Audio Siar Keluar Sekejap mengupas kesan domino yang tercetus selepas kekalahan mendalam Kerajaan Madani di PRN Sabah. Perbincangan merangkumi tekanan politik yang semakin memuncak apabila DAP menetapkan tempoh enam bulan kepada Perdana Menteri, Dato' Seri Anwar Ibrahim untuk melaksanakan reformasi, desakan dalaman daripada saudara Rafizi berhubung isu integriti, serta kegagalan komunikasi kerajaan dalam menyampaikan inisiatif dan menguasai naratif kepada rakyat.Episod ini juga meneliti spekulasi mengenai rombakan Kabinet yang dijangka dilakukan oleh Perdana Menteri, Dato' Seri Anwar Ibrahim, dalam masa terdekat dan bagaimana langkah tersebut boleh mengubah hala tuju politik nasional.Turut dianalisis ialah krisis dalaman Barisan Nasional, susulan keputusan MIC meluluskan usul keluar BN serta pendirian MCA yang bersedia berbuat demikian sekiranya UMNO memilih bekerjasama dengan DAP. Ketidaktentuan dalam BN ini menimbulkan persoalan besar tentang masa depan gabungan itu dan peranan UMNO dalam landskap politik negara.Ingin jenama anda dikenali oleh ribuan pendengar? Taja episod Keluar Sekejap 2026!Hubungi +6011-1919 1783 atau emel commercial@ksmedia.my

La seccion de Natalia Hernandez en La Brujula donde desdena con datos y cifras fenomenos sociales como el sorteo navideno.

La SER supera a COPE en 1.347.000 oyentes y duplica la audiencia de Onda Cero, según los datos de la tercera ola del EGM en 2025, que señala que la SER amplía su liderazgo de la radio en España con 4.892.000 oyentes y logra su mejor dato en los últimos 12 años. Hoy por Hoy amplía aún más su liderazgo en las mañanas con una audiencia de 3.405.000 oyentes y marca su récord histórico. Supera en casi 900.000 oyentes al segundo espacio radiofónico, Herrera en COPE, y suma un millón seiscientos mil oyentes por encima de Más de Uno de Onda Cero, que sigue siendo la tercera opción.

En el episodio de hoy de VG Daily, Andre Dos Santos y Juan Manuel de los Reyes exploran tres historias que revelan hacia dónde se mueve la economía global y la tecnología. Arrancan con la sorpresiva compra de Confluent por parte de IBM, una apuesta de once mil millones de dólares que marca cómo la infraestructura de datos en tiempo real se está convirtiendo en el nuevo corazón de la inteligencia artificial. Desde ahí saltan a China, donde las exportaciones hacia Estados Unidos se desplomaron en noviembre, un movimiento que pone en contexto el impacto acumulado de la tensión arancelaria y el reacomodo de cadenas de suministro. Para cerrar, analizan las nuevas multas de la Unión Europea contra X, parte de una tendencia creciente de sanciones a Big Tech y discuten si esta ola regulatoria está empezando a frenar la innovación en la región. Un episodio que conecta tecnología, geopolítica y regulación para entender el mapa económico que viene.

Volvemos a vuestros podcatchers con un capítulo donde Fer nos cuenta cómo el mundo ha conspirado para que tenga que comprarse unos AirPods Pro 3. Nos cuenta también alguna compra de software (como Dato de Sindre Sorhus) que ha hecho últimamente y, aunque dejará de dar el coñazo con Evernote, parece que ahora empezará a hacerlo con Craft.Siguiendo con el software, comentamos la curiosa manera de añadir soporte para podcasts en la aplicación Readwise Reader.Por su parte, Lucas nos cuenta cómo necesita chutes de adrenalina en su vida y los consigue con apuestas cada vez más arriesgadas en sus ventanas a través de Wallapop.Por último, recuperamos nuestra vieja sección de videojuegos para señores mayores, en la que Lucas nos cuenta su experiencia con la Nintendo Switch 2 y Fer nos habla de una jugada de Sony con los periodos de renovación de sus suscripciones.Capítulos del podcast00:00 Intro03:11 AirPods Pro 319:22 Un Black Friday de software23:00 Adiós Evernote, hola Craft29:52 Podcasts en Readwise Reader32:25 Lucas se la juega en Wallapop41:00 Videogarmers a los 4056:20 Offtopic: la jugada del Imserso01:02:58 DespedidaMétodos de contactoRecordad que podéis contactar con nosotros:* En Mastodon: @doalvares, @heyazorin y @calvocast* En el blog www.calvocast.com tenéis el feed del podcast y otras redes y formas de contactoSi te gusta lo que hacemos y nos lo quieres agradecer de alguna manera, puedes dejarnos un comentario en el blog sobre cualquiera de los temas que tratamos o también puedes dejarnos una reseña en Apple Podcasts, en Spotify o en tu podcatcher favorito. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit www.calvocast.com

Keluar Sekejap turun ke Kulim untuk episod khas sempena Karnival Literasi Tenaga yang dianjurkan oleh NUR Power bagi menyokong agenda Malaysia Energy Literacy Program (MELP) iaitu salah satu inisiatif nasional dari Kementerian Peralihan Tenaga dan Transformasi Air (PETRA) pada 29 November lalu!Dalam episod ini, Keluar Sekejap menemubual Dato' Haji Mohd Sahil bin Zabidi, Group CEO, Kulim Technology Park Corporation Sdn. Bhd. Beliau berkongsi pandangan eksklusif tentang masa depan KHTP, strategi menarik pelaburan, dan bagaimana Kedah boleh memimpin ekonomi hijau Malaysia.Keluar Sekejap juga mengupas masa depan tenaga Malaysia khususnya KHTP, pusat industri yang bergantung kepada NUR Power, satu-satunya utiliti bebas dengan rekod kebolehpercayaan bertaraf dunia.Ingin jenama anda dikenali oleh ribuan pendengar? Ingin menjemput Keluar Sekejap untuk Live Show?Taja episod Keluar Sekejap 2025!Hubungi +6011-1919 1783 atau emel commercial@ksmedia.my

Analizamos los datos de la última actualización del Censo Anual de Población de España del INE, que confirman el crecimiento de la población española gracias a la inmigración. Con el sociólogo Diego Gastón trasladamos esta información a la realidad social en la que vivimos. Además, conocemos las reivindicaciones y el estado de las viudas aragonesas con Lola Pueyo, presidenta de la Federación Regional de Asociaciones de Viudas de Aragón y de la Asociación de Mujeres Viudas Somontano de Barbastro.

La periodista Natalia Hernandez expone en su seccion en La Brujula como ha cambiado el mundo tras la llegada de la inteligencia artificial a nuestras vidas.

Adrien Rabiot continua a essere uno dei perni del centrocampodel Milan e anche contro l'Inter lo ha dimostratoDiventa un supporter di questo podcast: https://www.spreaker.com/podcast/radio-rossonera--2355694/support.

Audio Siar Keluar Sekejap Episod 179 menampilkan Dato' Seri Amirudin Shari, Menteri Besar Selangor, meneliti intipati Belanjawan Selangor 2026, termasuk keutamaan pendidikan negeri, strategi pembangunan ekonomi, serta komitmen terhadap kebajikan rakyat.Perbincangan turut menyentuh dinamika politik pasca Pemilihan PKR, termasuk isu perpecahan dalaman, persaingan kepimpinan, serta naratif “Hiruk dan Damai” yang terus membentuk perjalanan parti pada era semasa.Episod ini juga merungkai perkembangan terkini PRN Sabah, termasuk implikasinya terhadap politik nasional dan hubungan antara kerajaan negeri serta persekutuan.Selain itu, Dato' Seri Amirudin memberi respons terhadap dakwaan mengenai konsesi parkir yang dikaitkan dengan kerabat Selangor, serta isu melibatkan pegawai Menteri Besar yang didakwa hidup mewah.Ingin jenama anda dikenali oleh ribuan pendengar? Taja episod Keluar Sekejap 2025!Hubungi +6011-1919 1783 atau emel commercial@ksmedia.my.TIMESTAMP00:00 Intro 1:20 Refleksi EP Toh Puan Naimah5:00 Refleksi EP Zafrul7:40 Belanjawan Selangor 202611:15 Pendidikan Selangor20:33 Fokus Ekonomi Semikonduktor30:36 Tenaga Nuklear35:45 Sektor Baru Ekonomi Selangor38:20 Reformasi PBT44:25 Pendapatan Kerajaan Selangor48:35 PRN Sabah1:07:33 Masalah Dalaman PKR1:28:46 Nurul Izzah Bakal MB Selangor?1:35:45 Isu Konsesi Parkir1:45:50 Isu Pegawai MB

Antonio Naranjo habla sobre ello en 'Mr Dato'

El 20% de los menores en España ve porno antes de los 10 años. Además, en 7 de cada 10 hogares no se habla nunca o casi nunca de sexo. Lo analizamos con Pablo Ortiz, educador social e investigador y Silberio Sáez, sexólogo de AMALTEA

Explica Naranjo que "nadie dar por descartado que en estos episodios de la corrupción no estemos a mitad de publicación"

La iniciativa, explica Naranjo, se trata de una propuesta del gobierno popular que incluye ideas de la oposición, acuerda rechazar el alzamiento militar, reconocer moralmente a los perdedores de la guerra, ayudar económicamente a exiliados y niños de la guerra

Da tanto volevo soffermarmi su come, da un punto di vista statistico, riusciamo (o meno) a contare i femminicidi. Finalmente sono riuscito a trovare la persona l'ospite perfetta! Donata Columbro, giornalista e esserta di femminismo del dato, ci accompagna in questa analisi, in dialogo col vostro antropologo di fiducia.Libri consigliati:"lo stile dell'abuso" Raffaella Scarpa"Invisibili"  Caroline Criado-Perez"L'anniversario" Andrea BajaniDonata Columbro"Perché contare i femminicidi è un atto politico" - LibroIGAntropoché?IGSitoSe volete supportare il podcast potete donare un caffè simbolico alla pagina ko-fi

Enrique Quintana

Lo analiza Antonio Naranjo a raíz de la visita de los Reyes a China

Zaragoza tiene 14.982 semáforos, algunos de los cuales se convertirán en inteligentes en un proyecto pionero para regular el flujo real de peatones y coches, reducir los accidentes de tráfico y las emisiones a la atmósfera.

Conviértete en un seguidor de este podcast: https://www.spreaker.com/podcast/el-mananero-radio--3086101/support.

Serenis è il tuo centro medico per il benessere fisico e mentale. Rispondi al questionario di Serenis per essere associato al terapeuta più adatto a te. Attraverso questo link  puoi iniziare il percorso a prezzo agevolato, partendo da un colloquio conoscitivo gratuito. #adv

Federico comenta con Luis F. Quintero las causas del aumento del precio de la vivienda y la victoria de Milei.

Diventa un supporter di questo podcast: https://www.spreaker.com/podcast/radio-rossonera--2355694/support.

Maracanà con Marco Piccari e Stefano Impallomeni. Ospiti: Orlando:" Serve Spalletti alla Juve. La Lazio scintilla importante." DI Gennaro:" Sarri ha dato un'anima alla Lazio. La Roma ha un'idea" Bucchioni:"Tudor non andava confermato.

Enrique Quintana

En este episodio de VG Daily, Eugenio Garibay y Juan Manuel de los Reyes comienzan analizando el reporte más reciente de inflación, desglosando qué está pasando con los precios en energía, vivienda, bienes y servicios, y si la lectura sorprendió frente a las expectativas del mercado.De ahí pasan al frente corporativo con los reportes de Ford y Procter & Gamble, donde comentan los movimientos en volúmenes, márgenes y costos, así como las señales que las directivas dieron sobre el poder de precios y la demanda del consumidor.El episodio concluye con una lectura más amplia sobre lo que esto implica para la economía estadounidense, el consumo real, la presión sobre salarios y la trayectoria de las tasas de interés hacia los próximos meses.

San Siro non mancherà di dare il suo supporto al Milan in occasione delmatch contro il Pisa di questa sera: il record sugli spettatori mediDiventa un supporter di questo podcast: https://www.spreaker.com/podcast/radio-rossonera--2355694/support.

Sahibus Samahah Ustaz Haji Ahmad Fauwaz bin Dato' Ustaz Haji Fadzil, Mufti Wilayah Persekutuan (Mufti of the Federal Territories)

Escuche esta y más noticias de LA PATRIA Radio de lunes a viernes por los 1540 AM de Radio Cóndor en Manizales y en www.lapatria.com, encuentre videos de las transmisiones en nuestro Facebook Live: www.facebook.com/lapatria.manizales/videos

Summary del Show: • Wall Street retrocede ligeramente a la espera de nuevos resultados y del IPC. • $AAPL se acerca a los $4T de valuación impulsada por la demanda del iPhone 17. • $CNP vende su negocio de gas en Ohio por $2.6B para enfocarse en servicios regulados. • $PYPL amplía su participación en la alemana Shopware hasta el 41%.

El precio del oro supera por primera vez en la historia los 4.000 dólares por onza. Una subida del 49% que los expertos achacan a la incertidumbre y tensión geopolítica. ¿Cómo nos afecta en el día a día?.

Benvenuti in un viaggio affascinante attraverso il mondo delle lingue ibride - quelle lingue straordinarie che nascono quando due culture si incontrano e si mescolano. L'italiano è stato protagonista di tantissimi di questi incontri linguistici in giro per il mondo, creando fenomeni linguistici unici e sorprendenti che raccontano la storia dell'emigrazione italiana e dell'adattamento culturale. Lingue e Dialetti con Radici Italiane (Cocoliche, Chipilo...) Cosa Significa "Lingua Ibrida"? È molto semplice: immaginate di prendere due ingredienti diversi - come il sugo di pomodoro italiano e il piccante messicano - e di creare una salsa completamente nuova. Ecco, le lingue ibride funzionano proprio così! Quando comunità di immigrati si stabiliscono in nuovi Paesi, la loro lingua madre si mescola con quella locale, dando vita a forme comunicative uniche che portano in sé la storia, le sfide e l'ingegno di intere generazioni. Queste lingue sono nate principalmente grazie all'emigrazione italiana massiccia tra l'Ottocento e il Novecento, quando milioni di italiani hanno lasciato il loro paese per cercare fortuna nelle Americhe, in Australia e in altre parti del mondo. Portando con sé la loro lingua, i loro dialetti regionali e la loro cultura, gli emigrati italiani hanno dovuto adattarsi alle nuove realtà linguistiche, creando dei veri e propri "matrimoni linguistici" che ancora oggi ci stupiscono per la loro creatività e funzionalità. Dato sorprendente: Tra il 1876 e il 1976 circa 26 milioni di italiani hanno lasciato l'Italia. Questa migrazione di massa ha creato una rete globale di comunità italiane che hanno mantenuto viva la lingua attraverso adattamenti creativi e innovativi. Il Talian: Quando il Veneto Incontra il Portoghese Il Talian rappresenta una delle lingue ibride più affascinanti e meglio conservate al mondo. Nato nelle colline del Brasile meridionale, questo straordinario fenomeno linguistico racconta la storia di migliaia di veneti e trentini che hanno saputo reinventare la propria identità linguistica senza perderla. Le Origini Storiche del Talian Il Talian è nato nella seconda metà dell'Ottocento quando migliaia di veneti e trentini sono emigrati nel sud del Brasile, stabilendosi soprattutto negli stati di Rio Grande do Sul, Santa Catarina e Paraná. Questi coraggiosi emigrati si trovarono di fronte a una sfida duplice: dovevano comunicare non solo tra loro (ricordate che in Italia si parlavano principalmente dialetti regionali molto diversi tra loro), ma anche con i brasiliani di lingua portoghese e con immigrati di altre nazionalità. La necessità di sopravvivenza comunicativa portò alla nascita di questa lingua ibrida che combinava la base grammaticale veneta con un lessico sempre più arricchito da prestiti portoghesi. Gli immigrati mantenevano la struttura sintattica e fonetica della loro lingua madre, ma integravano parole portoghesi per concetti nuovi o per facilitare la comunicazione con i vicini brasiliani. Come Funziona il Talian Il Talian è sostanzialmente una base veneta con tantissimi prestiti dal portoghese, ma il meccanismo di fusione è molto sofisticato. La lingua mantiene la morfologia e la sintassi veneta, ma adatta il lessico alle esigenze del nuovo ambiente. Ecco alcuni esempi che mostrano questa incredibile creatività linguistica: Esempi pratici: • "Mi go comprado na machina nova" (Ho comprato una macchina nuova) • "Vamos ndar a la festa" (Andiamo alla festa) • "El tempo ze bon par trabalhar" (Il tempo è buono per lavorare) Notate come si mescola perfettamente? "Go" è veneto (ho), "comprado" è portoghese (comprato), "na" è veneto (una), "machina" è un adattamento, "nova" è portoghese! La bellezza del Talian sta proprio in questa fluidità naturale con cui integra elementi delle due lingue. Il Talian Oggi: Una Lingua Viva Incredibilmente, ancora oggi circa 500.000 persone parlano Talian in Brasile.

Las madres españolas, a la cabeza en ansiedad y agotamiento en la UE: el 78% están sobrecargadas. Acaban de presentar un estudio en el parlamento europeo.

Entérate de un dato curiosos que Yordi descubrió recientemente, es un dato que a todos nos debería importar y tendríamos que saber. ¡No se lo pierdan!See omnystudio.com/listener for privacy information.

El profesor de Sociología de la Universidad Complutense de Madrid ha analizado en Más de Uno los datos que recogió el CIS durante el verano respecto a este asunto. 

El profesor de Sociología de la Universidad Complutense de Madrid ha analizado en Más de Uno los datos que recogió el CIS durante el verano respecto a este asunto.