Podcasts about her2

Featuring perspectives from Dr Tanios Bekaii-Saab and Dr Kristen K Ciombor, including the following topics: Introduction: Assessment of HER2 Status (0:00) Case: An otherwise healthy woman in her early 50s with HER2-positive metastatic gallbladder cancer and multiple intrahepatic metastases — Jeremy Lorber, MD (7:33) Case: A man in his late 60s with HER2-low metastatic gallbladder cancer — Brian P Mulherin, MD (11:58) Data Review: Biliary Tract Cancers (18:19) Case: A man in his mid 50s with HER2-positive metastatic rectal cancer — Sunil Gandhi, MD (26:25) Case: A woman in her early 60s with recurrent HER2-positive rectal cancer — Ranju Gupta, MD (31:31) Data Review: Colorectal Cancer (34:16) Case: An otherwise healthy man in his mid 50s with HER2-positive metastatic gastroesophageal junction cancer and several metastatic liver lesions — Shachar Peles, MD (38:06) Case: A man in his early 60s with recurrent HER2-positive, claudin 18.2-positive metastatic esophageal cancer — Susmitha Apuri, MD (43:21) Data Review: Gastroesophageal Cancer (46:55) Case: A man in his early 60s with HER2-positive esophageal cancer and isolated brain metastases — Priya Rudolph, MD, PhD (50:07) CME information and select publications

Tonmya now available for fibromyalgia; safety warnings for DMD treatment; mitapivat shows mixed results in sickle cell disease trial; Redemplo approved for familial chylomicronemia syndrome; Hyrnuo approved for HER2-mutant NSCLC.

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 a landscape marked by significant scientific advancements, regulatory approvals, and strategic shifts that are reshaping the industry.Starting with Regeneron, the company's ophthalmic drug Eylea HD has recently secured two FDA approvals. These endorsements not only grant a new indication but also introduce a more flexible dosing regimen. This positions Eylea HD competitively against Roche's Vabysmo, highlighting the importance of regulatory navigation and strategic positioning in the pharmaceutical sector. These approvals come after extensive negotiations with both the FDA and third-party manufacturers, emphasizing the intricate processes involved in bringing a drug to market.In oncology, Bayer has achieved an accelerated FDA approval for Hyrnuo, a treatment targeting HER2-mutated non-small cell lung cancer. This move allows Bayer to challenge Boehringer Ingelheim's Hernexeos, underscoring the fiercely competitive nature of the oncology market. Such advancements are driven by innovative treatments that address specific genetic mutations in cancer patients, reflecting a broader trend towards precision medicine.Meanwhile, Moderna is investing heavily in mRNA production capabilities with a new $140 million facility in Norwood, Massachusetts. This development underscores Moderna's commitment to mRNA technology, which gained significant attention during the COVID-19 pandemic. The facility aims to establish robust domestic manufacturing infrastructures to mitigate supply chain vulnerabilities—a critical move considering recent global disruptions.Novartis is also making headlines with its plans for a flagship production hub in North Carolina. This expansion is expected to create 700 jobs and expand its manufacturing footprint by 700,000 square feet, highlighting Novartis's strategic emphasis on scaling up operations to meet growing demands and enhance production efficiency.In another strategic collaboration, Antheia has joined forces with Teva's TAPI division to enhance the commercialization prospects for its biosynthetic pipeline. This alliance marks a significant step toward advancing biologically derived pharmaceuticals, promising to revolutionize drug production through more sustainable and scalable alternatives to traditional chemical synthesis.On the regulatory front, Merck has received broad EU approval for a subcutaneous formulation of Keytruda. This development could significantly expand Keytruda's market reach across Europe, demonstrating how regulatory agility can extend drug lifecycles and maximize therapeutic impact across diverse patient populations.Compliance challenges remain prevalent, as illustrated by Pfizer and Tris Pharma's settlement of allegations related to ADHD medication Quillivant's quality control issues for $41.5 million. This case highlights ongoing efforts to ensure stringent quality standards within pharmaceutical manufacturing processes.Abbott is expanding its diagnostics portfolio through a $23 billion acquisition of Exact Sciences, known for its Cologuard colorectal cancer test. This acquisition indicates a strategic shift towards enhancing diagnostic capabilities alongside therapeutic offerings—a trend increasingly evident in holistic healthcare solutions.GSK is embarking on a $7 billion collaboration with biotechs Quotient and Profound through Flagship Pioneering. This partnership aims to leverage novel protein and genomic technologies to drive innovation in drug discovery and development, illustrating the industry's focus on integrating advanced biotechnological insights into traditional pharmaceutical frameworks.These developments collectively underscore crSupport the show

In this episode, Dr. Paul Wheatley-Price is back for our annual recap of the IASLC 2025 World Conference on Lung Cancer (WCLC), which took place in Barcelona, Spain in early September. He is joined by two special guests, Dr. Barbara Melosky, Professor of Medicine at UBC and Medical Oncologist at BC Cancer, and Dr. Peter Ellis, Professor of Oncology at McMaster University and Medical Oncologist at Juravinski Cancer Center. They chat about all the updates for treatments like osimertinib for EGFR+ lung cancer, immunotherapy for small-cell lung cancer, and promising new treatments like for HER2 and ADCs coming down the pipeline.

Send us a textFor our 100th episode, we explore how storytelling helps us reclaim body, mind, and spirit after cancer. Gillian Lichota, April Stearns, Melissa Andersen, and Sarah Zsak share how writing transforms fear into agency, supports embodiment, and creates space for healing and connection.Featured book: Rising Above: Our Transformational Journey to Wholeness After Breast CancerGillian Lichota – Founder/CEO of iRise Above Foundation, breast cancer thriver, adventure traveler, and lead author of Rising AboveApril Stearns – Founder/Editor of Wildfire Magazine; breast cancer survivor guiding expressive writing workshops. editor@wildfirecommunity.org IG: @wildfire_bc_magazine FB: facebook.com/wildfirecommunityMelissa Andersen – Former teacher turned nonprofit advocate; HER2+ survivor focused on healing, nature, & creativity. Substack: @melandersen IG: @ms_happyturtle FB: Melissa AndersenSarah Zsak – Speech-language pathologist, mom of four, Peace Corps alum, and Stage III survivor centered in faith, connection & hope. ResourcesPersonal Ink (P.ink Day): https://p-ink.org/p-ink-days/ ACS: Breast Cancer Facts & Figures: https://www.cancer.org/ Ohio State article on early signs of breast cancer: https://cancer.osu.edu/news/most-breast-cancers-dont-start-with-a-noticeable-lump Hopkins Reconstruction Surgeons: Dr. Lily Mundy – https://profiles.hopkinsmedicine.org/provider/lily-mundy/2700651 Dr. Nima Khavanin – https://profiles.hopkinsmedicine.org/provider/nima-khavanin/3052769Support the show Are you loving the Test Those Breasts! Podcast? You can show your support by donating to the Test Those Breasts Nonprofit @ https://testthosebreasts.org/donate/ Where to find Jamie:Instagram LinkedIn TikTok Test Those Breasts Facebook Group LinkTree Jamie Vaughn in the News! Thanks for listening! I would appreciate your rating and review where you listen to podcasts!I am not a doctor and not all information in this podcast comes from qualified healthcare providers, therefore may not constitute medical advice. For personalized medical advice, you should reach out to one of the qualified healthcare providers interviewed on this podcast and/or seek medical advice from your own providers .

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

Authors Drs. Jessica Ross and Alissa Cooper share insights into their JCO PO article, "Clinical and Pathologic Landscapes of Delta-Like Ligand 3 and Seizure-Related Homolog Protein 6 Expression in Neuroendocrine Carcinomas"  Host Dr. Rafeh Naqash and Drs. Ross and Cooper discuss the landscape of Delta-like ligand 3 (DLL3) and seizure-related homolog protein 6 (SEZ6) across NECs from eight different primary sites. 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'm your host, Dr. Rafeh Naqash, podcast editor for JCO PO and an Associate Professor at the OU Health Stephenson Cancer Center. Today, I'm excited to be joined by Dr. Jessica Ross, third-year medical oncology fellow at the Memorial Sloan Kettering Cancer Center, as well as Dr. Alissa Cooper, thoracic medical oncologist at the Dana-Farber Cancer Institute and instructor in medicine at Harvard Medical School. Both are first and last authors of the JCO Precision Oncology article entitled "Clinical and Pathologic Landscapes of Delta-like Ligand 3 and Seizure-Related Homolog Protein 6 or SEZ6 Protein Expression in Neuroendocrine Carcinomas." At the time of this recording, our guest disclosures will be linked in the transcript. Jessica and Alissa, welcome to our podcast, and thank you for joining us today. Dr. Jessica Ross: Thanks very much for having us. Dr. Alissa Cooper: Thank you. Excited to be here. Dr. Rafeh Naqash: It's interesting, a couple of days before I decided to choose this article, one of my GI oncology colleagues actually asked me two questions. He said, "Rafeh, do you know how you define DLL3 positivity? And what is the status of DLL3 positivity in GI cancers, GI neuroendocrine carcinomas?" The first thing I looked up was this JCO article from Martin Wermke. You might have seen it as well, on obrixtamig, a phase 1 study, a DLL3 bi-specific T-cell engager. And they had some definitions there, and then this article came along, and I was really excited that it kind of fell right in place of trying to understand the IHC landscape of two very interesting targets. Since we have a very broad and diverse audience, especially community oncologists, trainees, and of course academic clinicians and some people who are very interested in genomics, we'll try to make things easy to understand. So my first question for you, Jessica, is: what is DLL3 and SEZ6 and why are they important in neuroendocrine carcinomas? Dr. Jessica Ross: Yeah, good question. So, DLL3, or delta-like ligand 3, is a protein that is expressed preferentially on the tumor cell surface of neuroendocrine carcinomas as opposed to normal tissue. It is a downstream target of ASCL1, and it's involved in neuroendocrine differentiation, and it's an appealing drug target because it is preferentially expressed on tumor cell surfaces. And so, it's a protein, and there are several drugs in development targeting this protein, and then Tarlatamab is an approved bi-specific T-cell engager for the treatment of extensive-stage small cell lung cancer in the second line. SEZ6, or seizure-like homolog protein 6, is a protein also expressed on neuroendocrine carcinoma cell surface. Interestingly, so it's expressed on neuronal cells, but its exact role in neuroendocrine carcinomas and oncogenesis is actually pretty poorly understood, but it was identified as an appealing drug target because, similarly to DLL3, it's preferentially expressed on the tumor cell surface. And so this has also emerged as an appealing drug target, and there are drugs in development, including antibody-drug conjugates, targeting this protein for that reason. Dr. Alissa Cooper: Over the last 10 to 15 years or so, there's been an increasing focus on precision oncology, finding specific targets that actually drive the cancer to grow, not just within lung cancer but in multiple other primary cancers. But specifically, at least speaking from a thoracic oncology perspective, the field of non-small cell lung cancer has completely exploded over the past 15 years with the discovery of driver oncogenes and then matched targeted therapies. Within the field of neuroendocrine carcinomas, including small cell lung cancer but also other high-grade neuroendocrine carcinomas, there has not been the same sort of progress in terms of identifying targets with matched therapies. And up until recently, we've sort of been treating these neuroendocrine malignancies kind of as a monolithic disease process. And so recently, there's been sort of an explosion of research across the country and multiple laboratories, multiple people converging on the same open questions about why might patients with specific tumor biologies have different kind of responses to different therapies. And so first this came from, you know, why some patients might have a good response to chemo and immunotherapy, which is the first-line approved therapy for small cell lung cancer, and we also sort of extrapolate that to other high-grade neuroendocrine carcinomas. What's the characteristic of that tumor biology? And at the same time, what are other targets that might be identifiable? Just as Jesse was saying, they're expressed on the cell surface, they're not necessarily expressed in normal tissue. Might this be a strategy to sort of move forward and create smarter therapies for our patients and therefore move really into a personalized era for treatment for each patient? And that's really driving, I think, a lot of the synthesis of this work of not only the development of multiple new therapies, but really understanding which tumor might be the best fit for which therapy. Dr. Rafeh Naqash: Thank you for that explanation, Alissa. And as you mentioned, these are emerging targets, some more further along in the process with approved drugs, especially Tarlatamab. And obviously, DLL3 was something identified several years back, but drug development does take time, and readout for clinical trials takes time. Could you, for the sake of our audience, try to talk briefly about the excitement around Tarlatamab in small cell lung cancer, especially data that has led to the FDA approval in the last year, year and a half? Dr. Alissa Cooper: Sure. Yeah, it's really been an explosion of excitement over, as you're saying, the last couple of years, and work really led by our mentor, Charlie Rudin, had identified DLL3 as an exciting target for small cell lung cancer specifically but also potentially other high-grade neuroendocrine malignancies. Tarlatamab is a DLL3-targeting bi-specific T-cell engager, which targets DLL3 on the small cell lung cancer cells as well as CD3 on T cells. And the idea is to sort of introduce the cancer to the immune system, circumventing the need for MHC class antigen presentation, which that machinery is typically not functional in small cell lung cancer, and so really allowing for an immunomodulatory response, which had not really been possible for most patients with small cell lung cancer prior to this. Tarlatamab was tested in a phase 2 registrational trial of about 100 patients and demonstrated a response rate of 40%, which was very exciting, especially compared with other standard therapies which were available for small cell lung cancer, which are typically cytotoxic therapies. But most excitingly, more than even the response rate, I think, in our minds was the durability of response. So patients whose disease did have a response to Tarlatamab could potentially have a durable response lasting a number of months or even over a year, which had previously not ever been seen in this in the relapsed/refractory setting for these patients. I think the challenge with small cell lung cancer and other high-grade neuroendocrine malignancies is that a response to therapy might be a bit easier to achieve, but it's that durability. The patient's tumors really come roaring back quite aggressively pretty quickly. And so this was sort of the most exciting prospect is that durability of response, that long potential overall survival tail of the curve really being lifted up. And then most recently at ASCO this year, Dr. Rudin presented the phase 3 randomized controlled trial which compared Tarlatamab to physician's choice of chemotherapy in a global study. And the choice of chemotherapy did vary depending on the part of the world that the patients were enrolled in, but in general, it was a really markedly positive study for response rate, for progression-free survival, and for overall survival. Really exciting results which really cemented Tarlatamab's place as the standard second-line therapy for patients with small cell lung cancer whose disease has progressed on first-line chemo-immunotherapy. So that has been very exciting. This drug was FDA approved in May of 2024, and so has been used extensively since then. I think the adoption has been pretty widespread, at least in the US, but now in this global trial that was just presented, and there was a corresponding New England Journal paper, I think really confirms that this is something we really hopefully can offer to most of our patients. And I think, as we all know, that this therapy or other therapies like it are also being tested potentially in the first-line setting. So there was data presented with Tarlatamab incorporated into the maintenance setting, which also showed exciting results, albeit in a phase 1 trial, but longer overall survival than we're used to seeing in this patient population. And we await results of the study that is incorporating Tarlatamab into the induction phase with chemotherapy as well. So all of this is extraordinarily exciting for our patients to sort of move the needle of how many patients we can keep alive, feeling functional, feeling well, for as long as possible. Dr. Rafeh Naqash: Very exciting session at ASCO. I was luckily one of the co-chairs for the session that Dr. Rudin presented it, and I remember somebody mentioning there was more progress seen in that session for small cell lung cancer than the last 30, 35 years for small cell, very exciting space and time to be in as far as small cell lung cancer. Now going to this project, Jessica, since you're the first author and Alissa's the last, I'm assuming there was a background conversation that you had with Alissa before you embarked on this project as an idea. So could you, again, for other trainees who are interested in doing research, and it's never easy to do research as a resident and a fellow when you have certain added responsibilities. Could you give us a little bit of a background on how this started and why you wanted to look at this question? Dr. Jessica Ross: Yeah, sure. So, as with many exciting research concepts, I think a lot of them are derived from the clinic. And so I think Alissa and I both see a good number of patients with small cell, large cell lung cancer, and then high-grade neuroendocrine carcinomas. And so I think this was really born out of a basic conversation of we have these drugs in development targeting these two proteins, DLL3 and SEZ6, but really what is the landscape of cancers that express these proteins and who are the patients that really might benefit from these exciting new therapies. And of course, there was some data out there, but sort of less than one would imagine in terms of, you know, neuroendocrine carcinomas can really come from anywhere in the body. And so when you're seeing a patient with small cell of the cervix, for example, like what are the chances that their cancer expresses DLL3 or expresses SEZ6? So it was really derived from this pragmatic, clinically oriented question that we had both found ourselves thinking about, and we were lucky enough at MSK, we had started systematically staining patients' tumors for DLL3, tumors that are high-grade neuroendocrine carcinomas, and then we had also more recently started staining for SEZ6 as well. And so we had this nice prospectively collected dataset with which to answer this question. Dr. Rafeh Naqash: Excellent. And Alissa, could you try to go into some of the details around which patients you chose, how many patients, what was the approach that you selected to collect the data for this project? Dr. Alissa Cooper: This is perhaps a strength but also maybe a limitation of this dataset is, as Jesse alluded to, our pathology colleagues are really the stars of this paper here because we were lucky enough at MSK that they were really forethinking. They are absolute experts in the field and really forward-thinking people in terms of what information might be needed in the future to drive treatment decision-making. And so, as Jesse had said, small cell lung cancer tumor samples reflexively are stained for DLL3 and SEZ6 at MSK if there's enough tumor tissue. The other high-grade neuroendocrine carcinomas, those stains are performed upon physician request. And so that is a bit of a mixed bag in terms of the tumor samples we were able to include in this dataset because, you know, upon physician request depends on a number of factors, but actually at MSK, a number of physicians were requesting these stains to be done on their patients with high-grade neuroendocrine cancers of of other histologies. So we looked at all tumor samples with a diagnosis of high-grade neuroendocrine carcinoma of any histology that were stained for these two stains of interest. You know, I can let Jesse talk a bit more about the methodology. She was really the driver of this project. Dr. Jessica Ross: Yeah, sure. So we had 124 tumor samples total. All of those were stained for DLL3, and then a little less than half, 53, were stained for SEZ6. As Alissa said, they were from any primary site. So about half of them were of lung origin, that was the most common primary site, but we included GI tract, head and neck, GU, GYN, even a few tumors of unknown origin. And again, that's because I think a lot of these trials are basket trials that are including different high-grade neuroendocrine carcinomas no matter the primary site. And so we really felt like it was important to be more comprehensive and inclusive in this study. And then, methodologically, we also defined positivity in terms of staining of these two proteins as anything greater than or equal to 1% staining. There's really not a defined consensus of positivity when it comes to these two novel targets and staining for these two proteins. But in the Tarlatamab trials, for some of the correlative work that's been done, they use that 1% cutoff, and we just felt like being consistent with that and also using a sort of more pragmatic yes/no cutoff would be more helpful for this analysis. Dr. Alissa Cooper: And that was a point of discussion, actually. We had contemplated multiple different schemas, actually, for how to define thresholds of positivity. And I know you brought up that question before, what does it mean to be DLL3 positive or DLL3 high? I think you were alluding to prior that there was a presentation of obrixtamig looking at extra-pulmonary neuroendocrine carcinomas, and they actually divvied up the results between DLL3 50% or greater versus DLL3 low under 50%. And they actually did demonstrate differential efficacy certainly, but also some differential safety as well, which is very provocative and that kind of analysis has not been presented for other novel therapies as far as I'm aware. I could be wrong, but as far as I'm aware, that was sort of the first time that we saw a systematic presentation of considering patients to be, quote unquote, "high" or "low" in these sort of novel targets. I think it is important because the label for Tarlatamab does not require any DLL3 expression at all, actually. So it's not hinging upon DLL3 expression. They depend on the fact that the vast majority of small cell lung cancer tumors do express DLL3, 85% to 90% is what's been demonstrated in a few studies. And so, there's not prerequisite testing needed in that regard, but maybe for these extra-pulmonary, other histology neuroendocrine carcinomas, maybe it does matter to some degree. Dr. Rafeh Naqash: Definitely agree that this evolving landscape of trying to understand whether an expression for something actually really does correlate with, whether it's an immune cell engager or an antibody-drug conjugate is a very evolving and dynamically moving space. And one of the questions that I was discussing with one of my friends was whether IHC positivity and the level of IHC positivity, as you've shown in one of those plots where you have double positive here on the right upper corner, you have the double negative towards the left lower, whether that somehow determines mRNA expression for DLL3. Obviously, that was not the question here that you were looking at, but it does kind of bring into question certain other aspects of correlations, expression versus IHC. Now going to the figures in this manuscript, very nicely done figures, very easy to understand because I've done the podcast for quite a bit now, and usually what I try to do first is go through the figures before I read the text, and and a lot of times it's hard to understand the figures without reading the text, but in your case, specifically the figures were very, very well done. Could you give us an overview, a quick overview of some of the important results, Jessica, as far as what you've highlighted in the manuscript? Dr. Jessica Ross: Sure. So I think the key takeaway is that, of the tumors in our cohort, the majority were positive for DLL3 and positive for SEZ6. So about 80% of them were positive for DLL3 and 80% were positive for SEZ6. About half of the tumors were stained for both proteins, and about 65% of those were positive as well. So I think if there's sort of one major takeaway, it's that when you're seeing a patient with a high-grade neuroendocrine carcinoma, the odds are that their tumor will express both of these proteins. And so that can sort of get your head thinking about what therapies they might be eligible for. And then we also did an analysis of some populations of interest. So for example, we know that non-neuroendocrine pathologies can transform into neuroendocrine tumors. And so we specifically looked at that subset of patients with transformed tumors, and those were also- the majority of them were positive, about three-quarters of them were positive for both of these two proteins. We looked at patients with brain met samples, again, about 70% were positive. And then I'd say the last sort of population of interest was we had a subset of 10 patients who had serial biopsies stained for either DLL3 or SEZ6 or both. In between the two samples, these patients were treated with chemotherapy. They were not treated with targeted therapy, but interestingly, in the majority of cases, the testing results were concordant, meaning if it was DLL3 positive to begin with, it tended to remain DLL3 positive after treatment. And so I think that's important as well as we think about, you know, a patient who maybe had DLL3 testing done before they received their induction chemo-IO, we can somewhat confidently say that they're probably still DLL3 positive after that treatment. And then finally, we did do a survival analysis among specifically the patients with lung neuroendocrine carcinomas. We looked at whether DLL3 expression affected progression-free survival on first-line platinum-etoposide, and then we looked at did it affect overall survival. And we found that it did not have an impact or the median progression-free survival was similar whether you were DLL3 positive or negative. But interestingly, with overall survival, we found that DLL3 positivity actually correlated with slightly improved overall survival. These were small numbers, and so, you know, I think we have to interpret this with caution, for sure, but it is interesting. I think there may be something to the fact that five of the patients who were DLL3 positive were treated with DLL3-targeting treatments. And so this made me think of, like in the breast cancer world, for example, if you have a patient with HER2-positive disease, it initially portended worse prognosis, more aggressive disease biology, but on the other hand, it opens the door for targeted treatments that actually now, at least with HER2-positive breast cancer, are associated with improved outcomes. And so I think that's one finding of interest as well. Dr. Rafeh Naqash: Definitely proof-of-concept findings here that you guys have in the manuscript. Alissa, if I may ask you, what is the next important step for a project like this in your mind? Dr. Alissa Cooper: Jesse has highlighted a couple of key findings that we hope to move forward with future investigative studies, not necessarily in a real-world setting, but maybe even in clinical trial settings or in collaboration with sponsors. Are these biomarkers predictive? Are they prognostic? You know, those are still- we have some nascent data, data has been brewing, but I think that we we still don't have the answers to those open questions, which I think are critically important for determining not only clinical treatment decision-making, but also our ability to understand sequencing of therapies, prioritization of therapies. I think a prospective, forward-looking project, piggybacking on that paired biopsy, you know, we had a very small subset of patients with paired biopsies, but a larger subset or cohort looking at paired biopsies where we can see is there evolution of these IHC expression, even mRNA expression, as you're saying, is there differential there? Are there selection pressures to targeted therapies? Is there upregulation or downregulation of targets in response not just to chemotherapy, but for example, for other sort of ADCs or bi-specific T-cell engagers? I think those are going to be critically important future studies which are going to be a bit challenging to do, but really important to figure out this key clinical question of sequencing, which we're all contemplating in our clinics day in and day out. If you have a patient, and these patients often can be sick quite quickly, they might have one shot of what's the next treatment that you're going to pick. We can't guarantee that every patient is going to get to see every therapy. How can you help to sort of answer the question of like what should you offer? So I think that's the key question sort of underlying any future work is how predictive or prognostic are these biomarkers? What translational or correlative studies can we do on the tissue to understand clinical treatment decision-making? I think those are the key things that will unfold in the next couple of years. Dr. Rafeh Naqash: The last question for you, Alissa, that I have is, you are fairly early in your career, and you've accomplished quite a lot. One of the most important things that comes out from this manuscript is your mentorship for somebody who is a fellow and who led this project. For other junior investigators, early-career investigators, how did you do this? How did you manage to do this, and how did you mentor Jessica on this project with some of the lessons that you learned along the way, the good and other things that would perhaps help other listeners as they try to mentor residents, trainees, which is one of the important things of what we do in our daily routine? Dr. Alissa Cooper: I appreciate you calling me accomplished. Um, I'm not sure how true that is, but I appreciate that. I didn't have to do a whole lot with this project because Jesse is an extraordinarily smart, driven, talented fellow who came up with a lot of the clinical questions and a lot of the research questions as well. And so this project was definitely a collaborative project on both of our ends. But I think what was helpful from both of our perspectives is from my perspective, I could kind of see that this was a gap in the literature that really, I think, from my work leading clinical trials and from treating patients with these kinds of cancers that I really hoped to answer. And so when I came to Jessica with this idea as sort of a project to complete, she was very eager to take it and run with it and also make it her own. You know, in terms of early mentorship, I have to admit this was the first project that I mentored, so it was a great learning experience for me as well because as an early-career clinician and researcher, you're used to having someone else looking over your shoulder to tell you, "Yes, this is a good journal target, here's what we can anticipate reviewers are going to say, here are other key collaborators we should include." Those kind of things about a project that don't always occur to you as you're sort of first starting out. And so all of that experience for me to be identifying those more upper-level management sort of questions was a really good learning experience for me. And of course, I was fantastically lucky to have a partner in Jesse, who is just a rising star. Dr. Jessica Ross: Thank you. Dr. Rafeh Naqash: Well, excellent. It sounds like the first of many other mentorship opportunities to come for you, Alissa. And Jessica, congratulations on your next step of joining and being faculty, hopefully, where you're training. Thank you again, both of you. This was very insightful. I definitely learned a lot after I reviewed the manuscript and read the manuscript. Hopefully, our listeners will feel the same. Perhaps we'll have more of your work being published in JCO PO subsequently. Dr. Alissa Cooper: Hope so. Thank you very much for the opportunity to chat today. Dr. Jessica Ross: Yes, thank you. This was great. Dr. Rafeh Naqash: 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 as 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. Disclosures: Dr. Alissa Jamie Cooper Honoraria Company: MJH Life Scienes, Ideology Health, Intellisphere LLC, MedStar Health, Physician's Education Resource, LLC,  Gilead Sciences, Regeneron, Daiichi Sankyo/Astra Zeneca, Novartis,  Research Funding: Merck, Roche, Monte Rosa Therapeutics, Abbvie, Amgen, Daiichi Sankyo/Astra Zeneca Travel, Accommodations, Expenses: Gilead Sciences

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 a host of transformative events reshaping the landscape, from strategic acquisitions and funding infusions to regulatory maneuvers and scientific breakthroughs.Johnson & Johnson has taken a decisive step in its oncology strategy with the $3 billion acquisition of Halda's cell death technology. This acquisition, focusing on the "hold and kill" bifunctional small molecule platform, is poised to enhance J&J's prostate cancer pipeline significantly. It underscores J&J's commitment to expanding its oncology portfolio through innovative platforms designed to improve therapeutic outcomes. The move highlights a broader industry trend toward personalized medicine and targeted cancer therapies, which are becoming pivotal in improving patient care.In another domain of cancer treatment, Nuvalent has unveiled promising Phase 1/2 data for its candidate neladalkib, which could position the company as a formidable competitor to Pfizer's established lung cancer drug, Lorbrena. The promising data might expedite regulatory discussions with the FDA, potentially leading to an accelerated approval process. This development illustrates the competitive landscape in oncology, where firms strive to introduce novel therapies with improved efficacy and safety profiles.The field of antibody-drug conjugates (ADCs) is also experiencing significant advancements. A San Diego-based biotech has secured $120 million in funding to develop a best-in-class ADC formula, with support from Merck & Co. This initiative aims to refine the precision and efficacy of ADCs by delivering cytotoxic agents directly to cancer cells while minimizing collateral damage to healthy tissues. Such innovations are crucial as they represent a new frontier in targeted cancer therapy.In terms of financial activities, Artios Pharma's successful $115 million Series D funding round is set to bolster its clinical efforts in exploring DNA damage response inhibitors for cancer treatment. These inhibitors target cancer cells' ability to repair DNA damage, holding potential for more effective therapies against resistant cancer types. Meanwhile, Sofinnova Partners' €650 million raise for biotech and medtech investments amid a volatile economic environment underscores continued investor confidence in life sciences despite market uncertainties.Bayer is making strategic moves in China by opening an incubator in Beijing. This facility will host local biopharma companies such as Suzhou Puhe Biopharma and Beijing Youngen Technology, fostering innovation and collaboration within China's burgeoning biotech landscape. Such initiatives reflect global efforts to leverage regional strengths and foster cross-border collaborations.On the operational side, Nxera Pharma is restructuring its workforce by laying off 15% of its staff as part of a strategic pivot towards profitability. This decision mirrors broader industry trends where companies refocus resources on core projects to streamline operations and enhance financial stability.A recent study has highlighted the impact of NIH grant cuts on clinical trials across the United States. Over 383 trials involving more than 74,000 patients have been disrupted due to funding terminations under the current administration. This situation raises concerns about the sustainability of clinical research funding and its implications for ongoing medical advancements.Jazz Pharmaceuticals has reported practice-changing Phase 3 results for its HER2-targeted drug Ziihera for gastroesophageal adenocarcinoma. These findings reaffirm Jazz's confidence in positioning Ziihera as a preferred first-line treatment option for HER2-positive cancers, poSupport the show

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're diving into a myriad of pivotal changes and advancements that have been shaping our industry.The competitive nature of acquisitions within the biopharma sector has been exemplified by recent strategic buyouts. Lundbeck's decision to outbid Alkermes for Avadel Pharmaceuticals highlights how companies are leveraging acquisitions to expand their capabilities and portfolios. Similarly, Pfizer's finalized acquisition of Metsera after a fierce bidding war with Novo Nordisk underscores the importance of securing valuable assets to strengthen positioning in critical therapeutic areas, such as obesity treatment, where demand continues to rise.Regulatory milestones remain at the heart of industry progress. Organon and Henlius's Poherdy recently received FDA approval as a biosimilar to Roche's Perjeta, offering a new treatment avenue for HER2-positive breast cancer patients. This approval is noteworthy as biosimilars play an essential role in oncology by providing similar efficacy to original biologics but at reduced costs, thereby enhancing healthcare affordability and accessibility. In Europe, the EMA's Committee for Medicinal Products for Human Use has endorsed several innovative drugs, including Otsuka's Dawnzera for hereditary angioedema and Lilly's Inluriyo for certain cancer types. These endorsements reflect the growing pipeline of treatments addressing both rare genetic disorders and widespread diseases.Merck & Co.'s acquisition of Cidara Therapeutics for $9.2 billion underscores a strategic pivot towards bolstering its antiviral portfolio. This deal is particularly significant given Cidara's promising influenza antiviral candidate, initially abandoned by Johnson & Johnson. In an era where infectious diseases pose ever-evolving challenges, Merck's investment in antivirals reflects a commitment to advancing therapeutic solutions in this crucial area.However, drug development's inherent uncertainties were highlighted by Bristol Myers Squibb and Johnson & Johnson's joint anticoagulant venture, which faced termination due to a Phase 3 trial failure. This setback emphasizes the challenges and risks entailed in developing novel therapeutics, particularly within high-stakes areas like cardiovascular health.Leadership changes can significantly impact corporate strategy, as seen with Bavarian Nordic following an unsuccessful private equity takeover attempt. Such shifts can influence investor confidence and reshape strategic directions.Investment trends also paint an optimistic picture for innovation within the sector. European life sciences investor Medicxi's successful raising of €500 million signifies robust financial support for biotech ventures. This influx of capital is vital for propelling early-stage research and development efforts across Europe, fostering breakthroughs in chronic and rare disease treatments.In terms of scientific innovation, advancements in bispecific antibody production through AI/ML-driven molecular design promise higher yields and enhanced quality. These technological innovations could revolutionize complex biologics manufacturing, potentially accelerating timelines and expanding therapeutic possibilities.The regulatory landscape is seeing significant activity as well. Notably, FDA officials introduced a novel pathway aimed at accelerating gene editing therapies' development and approval. By facilitating faster market entry for personalized medicines, this regulatory innovation could pave the way for treatments tailored to individual genetic profiles.Kyowa Kirin's collaboration with Kura Oncology reached a milestone with FDA approval for an oral medication targeting acute myeloidSupport the show

"It's critical to identify those mutations found that are driving the cancer's growth and guide the personalized treatment based on those results. And important to remember, too, early testing is crucial for patients with non-small cell lung cancer (NSCLC). In studies, it has been found to be associated with improved survival outcomes and reduced mortality," ONS member Vicki Doctor, MS, BSN, BSW, RN, OCN®, precision medicine director at the City of Hope Atlanta, GA, Chicago, IL, and Phoenix, AZ, locations, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about the oncology nurse's role in NSCLC biomarker testing. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  This podcast is sponsored by Lilly Oncology and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications. Episode Notes  This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 363: Lung Cancer Treatment Considerations for Nurses Episode 359: Lung Cancer Screening, Early Detection, and Disparities Episode 238: Cancer Genomics for Every Oncology Nurse Episode 157: Biomarker Testing Improves Outcomes for Patients With Non-Small Cell Lung Cancer ONS Voice articles: Non-Small Cell Lung Cancer Prevention, Screening, Diagnosis, Treatment, Side Effects, and Survivorship Only a Third of Patients With Advanced Cancer Get Biomarker Testing, Limiting Use of Potentially Effective Precision Therapies Precision Medicine in Lung Cancer: How Comprehensive Testing Optimizes Patient Outcomes Targeted Therapies Are Transforming the Treatment of Non-Small Cell Lung Cancer ONS book: Guide to Cancer Immunotherapy (second edition) ONS course: Genomic Foundations for Precision Oncology Clinical Journal of Oncology Nursing article: Using Nurse Navigators to Improve Timeliness of Biomarker Testing for Non-Small Cell Lung Cancer Oncology Nursing Forum article: Precision Medicine Testing and Disparities in Health Care for Individuals With Non-Small Cell Lung Cancer: A Narrative Review Other ONS resources: Best Practices for Biomarker Testing in Non-Small Cell Lung Cancer: A Case Study Genomics and Precision Oncology Learning Library Genomics Case Study: Precision Medicine in the Setting of Metastatic Non-Small Cell Lung Cancer Biomarker Database (refine by non-small cell lung cancer) Genomic Biomarkers Huddle Card Targeted Therapy Huddle Card National Comprehensive Cancer Network homepage To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org Highlights From This Episode "These biomarkers are used to provide information about cancer's characteristics or behavior. In oncology precision medicine specifically, molecular tests can help with diagnosing a cancer that is maybe an unknown primary. It can help with monitoring response to therapy, detect recurrence of disease before other tests can find that, predict prognosis or how aggressive the cancer may be, and guide treatment decisions for targeted therapies." TS 3:14 "Some of the key biomarkers recommended by the National Comprehensive Cancer Network (NCCN) to be tested in patients who have NSCLC are EGFR, ALK, KRAS, BRAF, MET exon 14 skipping mutation, HER2 which is a protein expression from an ErbB protein, PD-L1 which is a protein expression that's used to guide immunotherapy choices, and then finally there are three fusions: ROS1, RET, and NTRK. [These] are pretty rare but really important to be tested for in patients who have NSCLC." TS 3:46 "Another important challenge for nurses related to this topic is that these results may not reveal a targeted mutation for the patient and that could be very disappointing. So, being able to provide that emotional support to a patient if they have that result … you can actually reinforce with them that if [they] go onto another treatment that the physician decides to put [them] on, the tumor can change. New pathogenic variants can develop based on the treatment that they're getting, and another test can be done. And maybe at that time—a new biomarker that could be targeted—we'd be seeing on the new test." TS 7:32  "Another circumstance we didn't talk about yet is that maybe the result came back saying that the quality was not sufficient. And sometimes that happens, but that doesn't mean that we're at the end of the road, necessarily. So, you could explain to the patient that that may mean that possibly, a new biopsy would be ordered by the physician. Or if a new biopsy or another tissue sample is not available, then maybe the physician would pivot to sending a blood specimen for the molecular testing. So that would definitely be a way [nurses] could support their patients." TS 11:52 "In the case of patients with NSCLC, early testing is so important. So, advocating for that prompt biomarker testing to be done, making sure that it's comprehensive, that it's actually looking for all of those—I think it was 12 biomarkers—that I mentioned earlier. That this testing is done as soon as possible after diagnosis or progression. Something that I talk about all the time—personalized care, precision medicine—really matters. So, tailoring treatments for patients based on the biology of the tumor that's driving the cancer's growth is really crucial if you're going to be working as an oncology nurse. Another crucial thing, because it's changing so quickly, is to stay informed." TS 16:23

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

In today's episode, filmed live at the 43rd Annual Chemotherapy Foundation Symposium, lung cancer expert Benjamin P. Levy, MD, hosted an in-depth discussion with Jonathan W. Lee, MD, MSc, on the evolving therapeutic landscape for EGFR-mutant and HER2-positive non–small cell lung cancer (NSCLC). Dr Levy is the clinical director of medical oncology at the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital and an associate professor of oncology at the Johns Hopkins University School of Medicine in Washington, DC. Dr Lee is the chief oncology/hematology fellow at Weill Cornell Medicine in New York, New York.

Love the episode? Send us a text!Inside the VIKTORIA-1 trial with Dr. Rachel LaymanWhat the New Genitolasib Data Mean for ER+ / HER2- Metastatic Breast CancerIn this episode of Breast Cancer Conversations, Laura sits down with Dr. Rachel Layman, breast medical oncologist at MD Anderson Cancer Center, to unpack what's new in ER-positive, HER2-negative metastatic breast cancer—and why clinical trials are not just a last-ditch option.Dr. Layman walks us through the VIKTORIA-1 trial, a phase III study of a new IV drug (genitolasib, “G” for short) that targets the PAM pathway, which cancer cells often use to grow and outsmart standard hormone therapy. She explains, in plain language, what PIC3CA mutations are, what “wild-type” means, and why this trial is so exciting even for people without a PIC3CA mutation.You'll hear:Why ER-positive breast cancer is the most common subtype—and still a major driver of metastatic diseaseHow clinical trials are designed, and why they're often most powerful earlier in treatment (not only when “nothing else is left”)A clear explanation of the VIKTORIA-1 study design: who was eligible, how the drug is given, and what the results showedWhat “progression-free survival” means and how adding “G” changed the numbers compared to standard therapy aloneHonest talk about side effects (mouth sores, rash, blood sugar changes), and how teams are preventing and managing themHow patients can look up trials like VIKTORIA-1 and VIKTORIA-2 on ClinicalTrials.gov and bring these conversations back to their own oncologistsWhether you're living with ER-positive metastatic breast cancer, supporting someone who is, or simply trying to understand the rapidly evolving science, this episode offers both education and hope.Support the showLatest News: Become a Breast Cancer Conversations+ Member! Sign Up Now. Join our Mailing List - New content drops every Monday!

Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago. In this episode, OncLive On Air® partnered with Two Onc Docs to review exciting updates from the 2025 ESMO Congress about bladder cancer management that have the potential to change guidelines. In non–muscle-invasive bladder cancer (NMIBC), 2 trials added immunotherapy to BCG. The phase 3 POTOMAC trial (NCT03528694) combining durvalumab (Imfinzi) with BCG for high-risk, BCG-naive NMIBC was positive, demonstrating improved disease-free survival with the combination. This regimen might become a new standard of care and could reduce the need for early radical cystectomy, the experts highlighted. For muscle-invasive bladder cancer, the phase 3 KEYNOTE-905 study (NCT03924895) combined perioperative enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) for cisplatin-ineligible patients. This positive trial demonstrated strong event-free survival and overall survival (OS) with the combination. Furthermore, the phase 3 IMvigor011 trial (NCT04660344) provided data on a risk-adapted approach using adjuvant atezolizumab (Tecentriq) for post-cystectomy patients with circulating tumor DNA (ctDNA)–positive disease. For these patients, atezolizumab generated benefits in disease-free survival and OS, supporting the future use of ctDNA for personalized therapy. Updates in metastatic bladder cancer emphasized the importance of testing for FGFR alterations and HER2 expression in the second-line setting, Armstrong and Tawagi explained. The phase 1 FORAGER-1 study (NCT05614739) showed the efficacy of an oral FGFR3 inhibitor in heavily pretreated patients and showed lower rates of hypophosphatemia with the agent compared with erdafitinib (Balversa). Overall, the conference yielded many new and exciting data points for the treatment of patients with bladder cancer.

Host: Jennifer Caudle, DO Guest: Samuel Klempner, MD Guest: Nataliya Uboha, MD, PhD Testing for biomarkers like PD-L1, HER2, claudin 18.2, and FGFR2b is reshaping our approach to first-line therapy in advanced gastric and gastroesophageal junction cancers. Alongside biomarker profiling, we must also weigh practical considerations around efficacy, toxicity, and patient-specific factors when selecting treatment. Joining Dr. Jennifer Caudle to explore how we can optimize our first-line treatment selection are Drs. Samuel Klempner and Dr. Nataliya Uboha. Dr. Klempner is an Associate Professor of Medicine at Harvard Medical School, and Dr. Uboha is an Associate Professor in the Division of Hematology and Oncology in the Department of Medicine at the University of Wisconsin.

Sanjay Popat, FRCP, PhD - Don't Forget About HER2: Clinical Insights and Novel Therapies for HER2-Mutant NSCLC From ESMO 2025

Sanjay Popat, FRCP, PhD - Don't Forget About HER2: Clinical Insights and Novel Therapies for HER2-Mutant NSCLC From ESMO 2025

Sanjay Popat, FRCP, PhD - Don't Forget About HER2: Clinical Insights and Novel Therapies for HER2-Mutant NSCLC From ESMO 2025

Sanjay Popat, FRCP, PhD - Don't Forget About HER2: Clinical Insights and Novel Therapies for HER2-Mutant NSCLC From ESMO 2025

Welcome to another episode of the Oncology Brothers podcast! In this episode, we are joined by Dr. Rami Manochakian from the Mayo Clinic to discuss the latest practice-changing studies presented at ESMO 2025, focusing on lung cancer. Episode Highlights: MDT-BRIDGE: Trial for resectable and borderline resectable non-small cell lung cancer (NSCLC) stressing the importance of a multidisciplinary approach. FLAURA2 Update: showcasing the overall survival benefits of osimertinib combined with chemotherapy for EGFR-positive NSCLC. SOHO-01 & Beamion LUNG-1: emerging HER2-positive NSCLC treatments, Zongertinib and Sevabertinib. Discussion on the significance of NGS testing in identifying mutations and tailoring treatment options for patients. Join us as we explore these important studies and their implications for improving patient outcomes in lung cancer care.  Follow us on social media: ⁠X/Twitter: https://twitter.com/oncbrothers ⁠Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ Don't forget to subscribe for more updates on practice-changing research and major conference highlights! #ESMO2025 #LungCancer #NSCLC #MDT #Zongertinib #Sevabertinib #Osimertinib #OncologyBrothers

Featuring perspectives from Dr Kathleen N Moore and Dr Matthew A Powell, including the following topics: Introduction: A Pan-tumor Perspective on Microsatellite Instability (MSI)-High Disease — Immunotherapy for Localized Disease (0:00) Case: A woman in her early 60s with mismatch repair-deficient metastatic endometrial cancer (EC) and multiple positive metastases — Shachar Peles, MD (8:18) Case: A woman in her mid 60s with recurrent EC and a BRCA mutation — Stephen "Fred" Divers, MD (12:17) Data Review: Immune Checkpoint Inhibitors (15:26) Case: A woman in her early 30s with Stage I mismatch repair-proficient EC and multiple pulmonary metastases after receiving fertility treatments — Kellie E Schneider, MD (28:22) Case: A woman in her early 80s with EC and high blood pressure — Syed F Zafar, MD (34:24) Case: A postmenopausal woman in her late 60s with recurrent HER2-positive EC and unresectable carcinomatosis — Lyndsay J Willmott, MD (38:18) Case: A woman in her late 60s with EC and pericarditis — Karim ElSahwi, MD (44:28) Data Review: Novel Antibody-Drug Conjugates (51:38) Case: A woman in her early 70s with metastatic MSI-stable, HER2-negative EC with PI3 kinase and FGFR mutations wants to avoid treatment with chemotherapy — Victoria Giffi, MD (55:01) CME information and select publications

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

Drs. Cooper and Rotow review the challenges of CNS involvement in HER2+ NSCLC, emphasizing the importance of baseline and ongoing brain imaging, and the emerging understanding of CNS penetrance for HER2-targeted therapies. They explore strategies for managing brain metastases, including balancing local therapies, including radiation with systemic treatments, and highlight the need for multidisciplinary approaches and further research on CNS activity in clinical trials.

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

A New England Journal of Medicine study showed a novel chemotherapy regimen, trastuzumab deruxtecan combined with pertuzumab, outperformed the current standard in treating HER2-positive advanced breast cancer, demonstrating better efficacy and tolerability with fewer traditional chemotherapy-related side effects. A JAMA Oncology study by Uppsala University revealed a modest increase in breast cancer risk with hormonal contraceptive use among over two million Swedish women, emphasizing the need for balanced counseling regarding risks and benefits. The REPAIR trial in Denmark, published in the British Medical Journal, demonstrated that a short course of antibiotics significantly reduced clinically important wound complications after vaginal delivery in women with episiotomies or second-degree tears, highlighting its potential benefit in postpartum care.

Drs. Rotow and Cooper explore the evolving landscape of HER2+ NSCLC treatment, highlighting recent advancements in targeted therapies like HER2 TKIs and antibody-drug conjugates. They emphasize the importance of comprehensive biomarker testing, the significance of personalized treatment approaches, and the exciting progress in providing more effective and tolerable second-line therapies for patients. The discussion underscores the field's movement toward precision medicine and the potential for future combination strategies and improved patient outcomes.

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

Drs. Cooper and Rotow discuss first-line treatment strategies for HER2+ NSCLC, highlighting the importance of comprehensive molecular testing and emerging targeted therapies. Key considerations include the efficacy of antibody-drug conjugates and TKIs, with ongoing clinical trials evaluating their potential as frontline treatments. The discussion emphasizes the need for personalized treatment approaches based on individual patient characteristics, molecular features, and the evolving landscape of HER2-targeted therapies.

In metastatic breast cancer, resistance to therapy remains one of the most challenging aspects to care. A key driver of resistance in hormone receptor-positive, HER2-negative disease is the ESR1 mutation, a genetic change that alters the estrogen receptor and limits the effectiveness of certain standard therapies. In this episode, CANCER BUZZ speaks with Eleonara Teplinsky, MD, FASCO, head of breast and gynecologic medical oncology at Valley-Mount Sinai Comprehensive Cancer Care, about how the ESR1 mutation shapes treatment decisions and explains communication strategies, such as the "lock-and-key" model. Then CANCER BUZZ speaks with Maimah Karmo, president and CEO of Tigerlily Foundation about the importance of communicating with patients in ways that foster clarity and compassion through relatable analogies. Guest: Eleonora Teplinsky, MD, FASCO Medical Oncologist Valley Mount Sinai Comprehensive Cancer Care Paramus, NJ Maimah Karmo President/CEO Tigerlily Foundation "If you had molecular testing of your tumor done at the time of diagnosis, that may not be enough. If there is disease progression, we might need to repeat it. So it's really important to stress that there are points in the disease course where we're going to be checking for these biomarkers." - Teplinsky "The more that we can know about the tumor, how it's going to behave, what treatment it may or may not respond to, really can help us." - Teplinsky "Having a physician that is a true partner with the patient, that has a relationship, that's trusted, and that feels safe and secure, it's really, really critical." - Karmo Resources: Unlocking the Conversation: Navigating ESR1 Mutations in Metastatic Breast Cancer

Drs. Lynce and Waks explore whether advances in HER2-targeted therapy are making metastatic HER2+ breast cancer potentially curable, highlighting long-term remissions, survival gains from trials, and ongoing studies testing treatment-free remission.

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

Are you ready for the evolving treatment paradigm in HER2-positive gastroesophageal adenocarcinoma (GEA) and biliary tract cancer (BTC)? Credit available for this activity expires: 10/24/27 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/her2-positive-gastroesophageal-adenocarcinoma-and-biliary-2025a1000sr3?&ecd=bdc_podcast_libsyn_mscpedu

Drs. Lynce and Waks discuss advances in early-stage HER2+ breast cancer, focusing on how targeted therapies have transformed outcomes. They explore de-escalation strategies, the role of platinum drugs, insights from the COMPASS trial, and the importance of pathologic complete response in guiding treatment decisions.

Send us a textYou can feel perfectly fine, hear the word cancer, and watch your whole life tilt. For Veronika Bubenickova, a seasoned product leader, that moment redefined how she approached work, wellness, and what it means to heal. We talk about the HER2+ whirlwind, the shock of chemo, the fatigue that steals sleep, and the mindset shift that turned treatment from a threat into an ally. Veronika shares the simple tools that helped her stay grounded through it all: nourishing food, gentle movement, intentional laughter, and anchoring herself in nature to restore joy and normalcy.Her greatest act of strength came through self-advocacy, asking hard questions, seeking the right specialists, and making choices that honored both her body and her future. Beyond the medical journey, Veronika opens up about the emotional and spiritual recovery that follows survival: naming the trauma that lingers, finding peace in uncertainty, and learning how to live fully again.Through Lotus Journey, she now helps other women navigate that same in-between, after treatment, before life feels steady again. Her book, Diary of a Soul Reborn, offers her hard-earned insights and a gentle path toward rebuilding identity, trust, and purpose. If you're ready to move from doom-scrolling to genuine healing, this conversation is your invitation.Contact Veronika:Mobile +44 (0)7538 462463  Email: info@veronika-bubenickova.comSocials: LinkedInYouTubeFacebookInstagram Are you loving the Test Those Breasts! Podcast? You can show your support by donating to the Test Those Breasts Nonprofit @ https://testthosebreasts.org/donate/ Where to find Jamie:Instagram LinkedIn TikTok Test Those Breasts Facebook Group LinkTree Jamie Vaughn in the News! Thanks for listening! I would appreciate your rating and review where you listen to podcasts!I am not a doctor and not all information in this podcast comes from qualified healthcare providers, therefore may not constitute medical advice. For personalized medical advice, you should reach out to one of the qualified healthcare providers interviewed on this podcast and/or seek medical advice from your own providers .

“We were able to show multiple datasets that actually deliver against this vision that antibody drug conjugates can improve on and therefore displace chemotherapy” says Dr. Susan Galbraith, AstraZeneca’s EVP of oncology R&D. Galbraith joins Bloomberg Intelligence analyst Sam Fazeli to break down key findings from ESMO — from early-line HER2 breast cancer data to progress in bladder and lung cancer. She details the promise of Enhertu and Datopotamab, AstraZeneca’s antibody-drug conjugates (ADCs), and how their work may transform cancer treatment in curative settings.See omnystudio.com/listener for privacy information.

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

This week's episode recaps some highlights from ESMO 2025: 1. Destiny-Breast05: T-DXd > T-DM1 in persistent HER2+ disease after neoadjuvant chemo + surgery 2. Keynote-905: Neoadjuvant Enfortumab Vedotin + pembro in cisplatin-ineligible bladder cancer 3. POTOMAC: Durvalumab + BCG in non-muscle invasive bladder cancer 4. IMvigor011: ctDNA-guided adjuvant atezolizumab in bladder cancer 5. Dynamic-III: ctDNA guide de-escalation or escalation of chemotherapy in stage III colon cancer 6. HARMONi-6: an excuse to talk about ivonescimab, a bispecific antibody unlike any other currently FDA approved

Did you know that approximately 50% of breast cancer patients who have been exposed to an aromatase inhibitor (AI) over time in the metastatic setting develop an ESR1 mutation? Credit available for this activity expires: 10/17/26 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1003008?ecd=bdc_podcast_libsyn_mscpedu

Featuring perspectives from Dr Aditya Bardia and Dr Adam M Brufsky, including the following topics: Introduction: Antibody-drug conjugates in localized breast cancer (0:00) Case: A frail woman in her late 70s with ER-positive, HER2-low metastatic breast cancer (mBC) receives sacituzumab govitecan after multiple lines of therapy — Eric Fox, DO (7:46) Case: A woman in her early 60s with NTRK-mutant ER-negative, HER2-low recurrent mBC receives trastuzumab deruxtecan — Lai (Amber) Xu, MD, PhD (21:07) Case: A woman in her mid 70s with PIK3CA-mutant recurrent metastatic triple-negative breast cancer who developed a diverticular abscess on neoadjuvant chemoimmunotherapy receives sacituzumab govitecan and pembrolizumab — Alan B Astrow, MD (31:49) Case: A woman in her mid 60s with ER-negative, HER2-low mBC receives sacituzumab govitecan after experiencing disease progression on capecitabine — Laila Agrawal, MD (38:37) Case: A woman in her late 50s with ER-negative, HER2-low mBC receives trastuzumab deruxtecan after experiencing disease progression on sacituzumab govitecan — Kimberly Ku, MD (44:24) Case: A woman in her early 60s with ER-positive, HER2-low mBC and hyperglycemia receives trastuzumab deruxtecan after experiencing disease progression on capivasertib/fulvestrant — Eleonora Teplinsky, MD (48:50) CME information and select publications

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

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into a series of major advancements and strategic moves that are shaping the future of healthcare.A significant development comes from AstraZeneca, which has committed a substantial $445 million investment to bolster production at its Texas facility for Lokelma, a treatment designed for hyperkalemia. Hyperkalemia is a condition characterized by elevated potassium levels in the blood, posing serious health risks if not managed properly. This investment highlights AstraZeneca's dedication to meeting growing global demand and enhancing patient access to this vital treatment. By strengthening its production capabilities, the company aims to ensure a more reliable supply chain, potentially leading to better outcomes for patients worldwide.Meanwhile, Pfizer is making noteworthy progress in the realm of oncology. Recent clinical trial results have positioned Tukysa, developed in collaboration with Seagen, as a promising candidate for first-line maintenance therapy in HER2-positive breast cancer. The potential shift from second-line to first-line treatment could significantly alter patient care by offering an effective therapeutic option earlier in the disease management process. This advancement underscores Pfizer's commitment to improving long-term outcomes for patients battling this aggressive form of cancer.In legal news, a dispute between Novo Nordisk and KBP Pharmaceuticals has underscored the critical importance of transparency and thorough due diligence in biotech transactions. The controversy involves "anomalous" phase 2 clinical trial results that Novo Nordisk claims were not adequately disclosed by KBP. Such cases highlight the necessity for rigorous investigation during mergers and acquisitions to prevent costly legal battles and ensure informed decision-making in drug development partnerships.On the HIV prevention front, GSK has released promising data for its long-acting pre-exposure prophylaxis drug, Apretude. This new data suggests Apretude holds higher acceptability compared to Gilead's competing product, Yetztugo. Improved patient adherence could shift market dynamics towards GSK's favor, potentially enhancing public health outcomes by preventing HIV infections more effectively.Manufacturing innovations are also taking center stage as Particle Dynamics collaborates with a former EuroAPI plant to introduce Codis, a new contract development and manufacturing organization (CDMO). Codis will offer comprehensive services such as spray drying and particle engineering, aligning with growing demand for specialized pharmaceutical manufacturing capabilities.Turning our attention to diabetes treatment advancements, Eli Lilly's oral GLP-1 candidate Orforglipron has demonstrated superiority over both placebo and AstraZeneca's Farxiga in phase 3 trials for type 2 diabetes. This success strengthens Eli Lilly's portfolio in a highly competitive market and could lead to regulatory approval next year. An oral treatment option could significantly enhance patient compliance compared to existing injectable GLP-1 therapies.In oncology, Boehringer Ingelheim has entered into a deal worth up to $991 million with AimedBio, focusing on antibody-drug conjugates (ADCs) that target proteins involved in tumor growth and resistance. This collaboration highlights the increasing interest in ADCs as targeted cancer therapies capable of minimizing systemic toxicity while delivering potent cytotoxic agents directly to cancer cells.The industry continues to be shaped by funding rounds and strategic acquisitions. Novo Nordisk's acquisition of Omeros' MASP-3 inhibitor Zaltenibart for $2.1 billion marks a significant move in rare disease therapeutics. Despite Omeros pausing development, Novo Nordisk sees potential in treating paroxysSupport the show

Featuring an interview with Dr Laura Huppert, including the following topics: General overview of antibody-drug conjugate (ADC) structure and function; mechanisms of resistance to ADCs (0:00) Preventing and managing toxicities associated with trastuzumab deruxtecan (5:44) Selecting between sacituzumab govitecan and datopotamab deruxtecan for patients with metastatic breast cancer; common toxicities associated with these 2 agents (9:30) Potential use of ADCs in the first line for metastatic triple-negative breast cancer (mTNBC) (16:13) Case: A woman in her mid 40s with mTNBC receives sacituzumab govitecan and pembrolizumab in the first-line setting (18:25) CNS penetration and activity of ADCs in the treatment of breast cancer (22:27) Use of trastuzumab deruxtecan for HER2-ultralow mTNBC; promising trials of ADCs and other therapies for mTNBC (24:24) Treatment options in the second line and beyond for patients with HR-positive mBC that is HER2-negative, HER2 low or HER2 ultralow (27:05) Case: A woman in her late 50s with HR-positive, HER2-low mBC experiences disease progression on multiple lines of therapy (30:51) Ongoing evaluation of ADCs in the localized disease setting (35:42) Novel therapeutic approaches for leptomeningeal disease in patients with breast cancer (38:38) CME information and select publications

In this episode I sit with Keia and she opens up about her journey with breast cancer, a complex diagnosis of 30% ER positive, triple negative, and HER2 negative. She gives us so much more information on doing our breast exam ans also that men get breast cancer as well.

Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Let's dive into the latest news shaping this dynamic industry.Bristol Myers Squibb recently made headlines with their acquisition of Orbital Therapeutics for a remarkable $1.5 billion. This strategic move is aimed at enhancing their in vivo cell therapy capabilities, particularly in treating autoimmune disorders. In vivo cell therapy is a pioneering approach that allows genetic modifications directly within a patient's body, potentially revolutionizing the treatment landscape for numerous conditions. This acquisition underscores Bristol Myers Squibb's commitment to pushing the boundaries of innovative cell therapy technologies and reflects a broader trend in the industry towards personalized medicine.In another significant development, AstraZeneca has aligned with the Trump administration's Most Favored Nation pricing program, agreeing to provide Medicaid drugs at prices competitive on a global scale. This decision marks a strategic shift towards cost reduction, especially in chronic disease management and respiratory therapeutics. The move is indicative of AstraZeneca's efforts to adapt to regulatory pressures and evolving policies that emphasize value-based healthcare delivery.Meanwhile, Ypsomed has announced plans to invest $248 million in establishing a manufacturing facility in North Carolina. This facility will focus on producing auto-injectors, essential for treating diabetes and metabolic disorders. The investment signifies a strategic operational expansion aimed at meeting rising demand in North America, highlighting the growing importance of drug delivery devices in the therapeutic landscape.Turning to clinical trials, Regeneron has unveiled promising Phase 1/2 data for its DB-OTO gene therapy targeting genetic hearing loss in children. By using AAV vectors to address DFNB9-related synaptic transmission deficits, this therapy could mark a breakthrough for those suffering from hereditary hearing conditions. Satellos has also presented encouraging Phase 1 results for SAT-3247, an oral small molecule targeting AAK1 in Duchenne muscular dystrophy, with plans to proceed to Phase 2 trials focused on muscle regeneration.In oncology, Taiho and Cullinan's Phase 2 data on zipalertinib showed efficacy against EGFR-mutated non-small cell lung cancer with brain metastases. This advancement highlights the potential of tyrosine kinase inhibitors in precision oncology. Similarly, Arcus Biosciences reported a median survival of 26.7 months for its combination therapy with domvanalimab and zimberelimab in gastroesophageal adenocarcinoma trials, underscoring the promise of TIGIT-targeted therapies.Assembly Biosciences has shared promising Phase 1b results for its ABI-5366 helicase-primase inhibitor, achieving an impressive 94% reduction in herpes simplex virus shedding. OS Therapies reported significant survival improvement with its OST-HER2 vaccine in recurrent pulmonary metastatic osteosarcoma patients, positioning HER2-targeting immunotherapies as promising cancer treatment interventions.Cabaletta Bio has made strides with its resecabtagene autoleucel CAR-T therapy, demonstrating B cell elimination without preconditioning in pemphigus vulgaris trials. This innovation opens new doors for autoimmune disease management through advanced cell therapies.On the business development front, Roche's out-licensing of its GLP-1/GIP agonist CT-388 to Chugai for diabetes and obesity treatment exemplifies strategic partnerships focused on addressing metabolic disorders through novel small molecules.The sector is also witnessing significant financial activities with Evommune filing an IPO to advance treatments for inflammatory conditions. Meanwhile, Quoin Pharmaceuticals raised $104.5 million through private placement to concentrate on rare disSupport the show

In this podcast episode, breast cancer experts Manali Bhave, MD, and Erin F. Cobain, MD, discuss their management of patients with HR-positive/HER2-negative early breast cancer including insights on identifying high-risk disease considering clinical/pathological factors and gene expression assays and answering healthcare professional questions on how to personalize adjuvant therapy for these patients. Supported by an educational grant from Lilly.Faculty:Manali Bhave, MDMedical Director, Phase I Clinical Trials UnitAssistant ProfessorDepartment of Hematology and OncologyWinship Cancer InstituteEmory UniversityAtlanta, GeorgiaErin F. Cobain, MDAssociate Professor of Internal MedicineDivision of Hematology/OncologyBreast Oncology ProgramUniversity of Michigan Rogel Cancer CenterAnn Arbor, Michigan Link to obtain CME/CE credit: https://bit.ly/46RvtgHLink to Oncology Breast Cancers with additional educational activities: https://bit.ly/4h7R3AO Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Dr. Hope Rugo and Dr. Giuseppe Curigliano discuss recent developments in the field of bispecific antibodies for hematologic and solid tumors, including strategies to optimize the design and delivery of the immunotherapy. TRANSCRIPT Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center. I am also the editor-in-chief of the Educational Book. Bispecific antibodies represent an innovative and advanced therapeutic platform in hematologic and solid tumors. And today, I am delighted to be joined by Dr. Giuseppe Curigliano to discuss the current landscape of bispecific antibodies and their potential to reshape the future of precision oncology. Dr. Curigliano was the last author of an ASCO Educational Book piece for 2025 titled, "Bispecific Antibodies in Hematologic and Solid Tumors: Current Landscape and Therapeutic Advances." Dr. Curigliano is a breast medical oncologist and the director of the Early Drug Development Division and chair of the Experimental Therapeutics Program at the European Institute of Oncology in Milan. He is also a full professor of medical oncology at the University of Milan. You can find our disclosures in the transcript of this episode. Dr. Curigliano, Giuseppe, welcome and thanks for being here. Dr. Giuseppe Curigliano: Thanks a lot for the invitation. Dr. Hope Rugo: Giuseppe, I would like to first ask you to provide some context for our listeners on how these novel therapeutics work. And then perhaps you could tell us about recent developments in the field of bispecific antibodies for oncology. We are at a time when antibody-drug conjugates (ADCs) are all the rage and, trying to improve on the targeting of specific antigens, proteins, receptors in the field of oncology is certainly a hot and emerging topic. Dr. Giuseppe Curigliano: So, thanks a lot. I believe really it was very challenging to try to summarize all the bispecific antibodies that are under development in multiple solid tumors. So, the first thing that I would like to highlight is the context and the mechanism of action of bispecific antibodies. Bispecific antibodies represent a groundbreaking advancement in cancer immunotherapy, because these engineered molecules have the unique ability to target and simultaneously bind to two distinct antigens. That is why we call them bispecific. So typically, one antigen is expressed on the tumor cell and the other one is expressed on the immune effectors, like T-cell or natural killer cells. So this dual targeting mechanism offers several key advantages over conventional monoclonal antibodies because you can target at the same time the tumor antigen, downregulating the pathway of proliferation, and you can activate the immune system. So the primary mechanism through which bispecific antibodies exert their therapeutic effects are: First, T-cell redirecting. I mean, many bispecific antibodies are designed to engage tumor-associated antigens like epidermal growth factor receptor, HER2, on the cancer cell and a costimulatory molecule on the surface of T-cell. A typical target antigen on T-cell is CD3. So what does it mean? That you activate the immune system, immune cells will reach the tumor bed, and you have a dual effect. One is downregulating cell proliferation, the other one is activation of the immune system. This is really important in hematological malignancies, where we have a lot of bispecifics already approved, like acute lymphoblastic leukemia or non-Hodgkin lymphoma.  The second, in fact, is the engagement of the tumor microenvironment. So, if you engage immune effector cells like NK cells or macrophages, usually the bispecific antibodies can exploit the immune system's ability to recognize and kill the immune cells, even if there is a lack of optimal antigen presentation.  And finally, the last mechanism of action, this may have a role in the future, maybe in the early cancer setting, is overcoming immune evasion. So bispecific antibodies can overcome some of the immune evasion mechanisms that we see in cancer. For example, bispecific antibodies can target immune checkpoint receptors, like PD-L1 and CTLA-4. Actually, there is a bispecific under development in breast cancer that has a dual targeting on vascular endothelial growth factor receptor and on PD-L1. So you have a dual effect at the same time. So, what is really important, as a comment, is we need to focus first on the optimal format of the bispecific, the optimal half-life, the stability, because of course even if they are very efficient in inducing a response, they may give also a lot of toxicities. So in clinical trials already, we have several bispecifics approved. In solid tumors, very few, specifically amivantamab for non-small cell lung cancer, but we have a pipeline of almost 40 to 50 bispecifics under development in multiple solid tumors, and some of them are in the context of prospective randomized trials. Dr. Hope Rugo: So this is really a fascinating area and it's really exciting to see the expansion of the different targets for bispecific antibodies. One area that has intrigued me also is that some of the bispecifics actually will target different parts of the same receptor or the same protein, but presumably those will be used as a different strategy. It's interesting because we have seen that, for example, in targeting HER2. Dr. Giuseppe Curigliano: Oh, yes, of course. You may consider some bispecifics like margetuximab, I suppose, in which you can target specifically two different epitopes of the same antigen. This is really an example of how a bispecific can potentially be more active and downregulating, let us say, a pathway, by targeting two different domains of a specific target antigen. This is an important point.  Of course, not all the bispecifics work this way, because some of the target antigen may dimerize, and so you have a family of target antigen; an example is epidermal growth factor receptor, in which you have HER1, HER2, HER3, and HER4. So some of them can inhibit the dimerization between one target antigen and the other one, in order to exert a more antiproliferative effect. But to be honest, the new generation of them are more targeting two different antigens, one on the tumor and one on the microenvironment, because according to the clinical data, this is a more efficient way to reduce proliferation and to activate the immune system. Dr. Hope Rugo: Really interesting, and I think it brings us to the next topic, which is really where bispecific antibodies have already shown success, and that is in hematologic malignancies where we have seen very interesting efficacy and these are being used in the clinic already. But the expansion of bispecific antibodies into solid tumors faces some key challenges. It's interesting because the challenges come in different shapes and forms. Tell us about some of those challenges and strategies to optimize bispecific antibody design, delivery, patient selection, and how we are going to use these agents in the right kind of clinical trials. Dr. Giuseppe Curigliano: This is really an excellent question because despite bispecific antibodies having shown a remarkable efficacy in hematological malignancies, their application in solid tumors may have some challenges. The first one is tumor heterogeneity. In hematological malignancy, you have a clear oncogene addiction. Let us say that 90% of the cells may express the same antigen. In solid tumors, it is not the same. Tumor heterogeneity is a typical characteristic of solid tumors, and you have high heterogeneity at the genetic, molecular, and phenotypic levels. So tumor cells can differ significantly from one another, even if within the same tumor. And this heterogeneity sometimes makes it difficult to identify a single target antigen that is universally expressed in an hematological malignancy. So furthermore, sometimes the antigen expressed on a tumor cell can be also present on the normal tissue. And so you may have a cross-targeting. So let's say, if you have a bispecific against epidermal growth factor receptor, this will target the tumor but will target also the skin with a lot of toxicity. The second challenge is the tumor microenvironment. The solid tumor microenvironment is really complex and often immunosuppressive. It is characterized by the presence of immunosuppressor cells like the T regulators, myeloid derived suppressor cells, and of course the extracellular matrix. All these factors hinder immune cell infiltration and also may reduce dramatically the effectiveness of bispecific antibodies. And as you know, there is also an hypoxic condition in the tumor. The other challenge is related to the poor tumor penetration. As you know also with antibody-drug conjugate, only 1 to 3% of the drug will arrive in the tumor bed. Unlike hematological malignancies where tumor cells are dispersed in the blood and easily accessible, the solid tumors have a lot of barriers, and so it means that tumor penetration can be very low. Finally, the vascularity also of the tumor can be different across solid tumors. That is why some bispecifics have a vascular endothelial growth factor receptor or vascular endothelial growth factor as a target. Of course, what do we have to do to overcome these challenges? First, we have to select the optimal antigen. So knowing very well the biology of cancer and the tumor-associated antigens can really select a subgroup of epitopes that are specifically overexpressed in cancer cells. And so we need to design bispecifics according to the tumor type. Second, optimize the antibody format. So there are numerous bispecific antibody formats. We can consider the dual variable domain immunoglobulin, we specified this in our paper. The single chain variable fragments, so FC variable fragments, and the diabodies that can enhance both binding affinity and stability. And finally, the last point, combination therapies. Because bispecific antibodies targeting immune checkpoint, we have many targeting PD-1 or PD-L1 or CTLA-4, combined eventually with other immune checkpoint inhibitors. And so you may have more immunostimulating effect. Dr. Hope Rugo: This is a fascinating field and it is certainly going to go far in the treatment of solid tumors. You know, I think there is some competition with what we have now for antibody-drug conjugates. Do you see that bispecifics will eventually become bispecific ADCs? Are we going to combine these bispecific antibodies with ADCs, with chemotherapy? What is the best combination strategy do you think looking forward? Dr. Giuseppe Curigliano: So, yes, we have a bispecific ADC. We have actually some bispecifics that are conjugated with a payload of chemotherapy. Some others are conjugated with immunoactivation agents like IL-2. One of the most effective strategies for enhancing bispecific activity is the combination therapy. So which type of combination can we do? First, bispecific antibodies plus checkpoint inhibitors. If you combine a bispecific with an immune checkpoint, like anti-PD-1, anti-PD-L1, or anti-CTLA-4, you have more activity because you have activation of T-cells, reduction of immunosuppressive effect, and of course, the capability of this bispecific to potentiate the activity of the immune checkpoint inhibitor. So, in my opinion, in a non-small cell lung cancer with an expression of PD-L1 more than 50%, if you give pembrolizumab plus a bispecific targeting PD-L1, you can really improve both response rate and median progression-free survival.  Another combination is chemotherapy plus bispecific antibodies. Combining chemotherapy with bispecific can enhance the cytotoxic effect because chemotherapy induces immunogenic cell death, and then you boost with a bispecific in order to activate the immune system. Bispecific and CAR T-cells, until now, we believe that these are in competition, but this is not correct. Because CAR T-cells are designed to deliver an activation of the immune system with the same lymphocytes engineered of the patients, with a long-term effect. So I really do not believe that bispecifics are in competition with CAR T-cells because when you have a complete remission induced by CAR T-cell, the effect of this complete remission can last for years. The activity of a bispecific is a little bit different. So there are some studies actually combining CAR T-cells with bispecifics. For example, bispecific antibodies can direct CAR T-cells in the tumor microenvironment, improving their specificity and enhancing their therapeutic effect.  And finally, monoclonal antibody plus bispecific is another next generation activity. Because if you use bispecific antibodies in combination with existing monoclonal antibodies like anti-HER2, you can potentially increase the immune response and enhance tumor cell targeting. In hematological malignancies, this has been already demonstrated and this approach has been particularly effective. Dr. Hope Rugo: That's just so fascinating, the whole idea that we have these monoclonal antibodies and now we are going to add them to bispecifics that we could maybe attach on different toxins to try and improve this, or even give them with different approaches. I suppose giving an ADC with a bispecific would sort of be similar to that idea of giving a monoclonal antibody with the bispecific. So it is certainly intriguing. We also will need to understand the toxicity and cost overall and how we are going to use these, the duration of treatment, the assessment of biomarkers. There are just so many different aspects that still need to be explored.  And then with that idea, can you look ahead five or ten years from now, and tell us how you think bispecific antibodies will shape our next generation cancer therapies, how they will be incorporated into precision oncology, and the new combinations and approaches as we move forward that will help us tailor treatment for patients both with solid tumors and hematologic malignancies? Are we going to be giving these in early-stage disease in solid tumors? So far, the studies are primarily focusing on the metastatic setting, but obviously one of the goals when we have successful treatments is to move them into the early stage setting as quickly as possible. Dr. Giuseppe Curigliano: Let us try to look ahead five years rather than ten years, to be more realistic. So, personally I believe some bispecifics can potentially replace current approaches in specifically T-cell selected population. As we gather more data from ongoing clinical trials and we adopt a deeper understanding of the tumor immuno microenvironment, of course we may have potentially new achievement. A few days ago, we heard that bispecifics in triple negative breast cancer targeting VEGF and PD-L1 demonstrated an improvement in median progression-free survival.  So, how to improve and to impact on clinical practice both in the metastatic and in the early breast cancer setting or solid tumor setting? First, personalized antigen selection. So we need to have the ability to tailor bispecific antibody therapy to the unique tumor profile of individual patients. So the more we understand the biology of cancers, the more we will be able to better target. Second, bispecific antibodies should be combined. I can see in the future a potential trial in which you combine a bispecific anti-PD-L1 and VEGF with immune checkpoint inhibitor selected also to the level of expression of PD-L1, because integration of antibody bispecific with a range of immunotherapies, and this cannot be only immune checkpoint inhibitors, but can be CAR T-cells, oncolytic viruses, also targeted therapy, will likely be a dominant theme in the coming years. This combination will be based on the specific molecular and immuno feature of the cancer of the patient.  Then we need an enhanced delivery system. This is really important because you know now we have a next generation antibody. An example are the bicyclic. So you use FC fragment that are very short, with a low molecular weight, and this short fragment can be bispecific, so can target at the same time a target antigen and improving the immune system. And so the development of this novel delivery system, including also nanoparticles or engineered viral vectors, can enhance the penetration in the tumor bed and the bioavailability of bispecific antibodies. Importantly, we need to reduce toxicity. Until now, bispecifics are very toxic. So the more we are efficient in delivering in the tumor bed, the more we will reduce the risk of toxicity. So it will be mandatory to reduce off-target effects and to minimize toxicity.  And finally, the expansion in new indication. So I really believe you raised an excellent point. We need to design studies in the neoadjuvant setting in order to better understand with multiple biopsies which is the effect on the tumor microenvironment and the tumor itself, and to generate hypotheses for potential trials or in the neoadjuvant setting or in those patients with residual disease.  So, in my opinion, as we refine design, optimize patient selection, and explore new combination, in the future we will have more opportunity to integrate bispecifics in the standard of care. Dr. Hope Rugo: I think it is particularly helpful to hear what we are going to be looking for as we move forward to try and improve efficacy and reduce toxicity. And the ability to engineer these new antibodies and to more specifically target the right proteins and immune effectors is going to be critical, of course, moving forward, as well as individualizing therapy based on a specific tumor biology.  Hearing your insights has been great, and it really has opened up a whole area of insight into the field of bispecifics, together with your excellent contribution to the ASCO Educational Book. Thank you so much for sharing your thoughts and background, as well as what we might see in the future on this podcast today. Dr. Giuseppe Curigliano: Thank you very much for the invitation and for this excellent interview. Dr. Hope Rugo: And thanks to our listeners for joining us today. You will find a link to the Ed Book article we discussed today in the transcript of this episode. It is also, of course, on the ASCO website, as well as on PubMed. Please join us again next month on By the Book for more insightful views on the key issues and innovations that are shaping modern oncology. 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. Follow today's speakers:       Dr. Hope Rugo  @hope.rugo  Dr. Giuseppe Curigliano @curijoey Follow ASCO on social media:       @ASCO on X (formerly Twitter)       ASCO on Bluesky      ASCO on Facebook       ASCO on LinkedIn       Disclosures:      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  Dr. Giuseppe Curigliano: Leadership: European Society for Medical Oncology, European Society of Breast Cancer Specialists, ESMO Open, European Society for Medical Oncology Honoraria: Ellipses Pharma Consulting or Advisory Role: Roche/Genentech, Pfizer, Novartis, Lilly, Foundation Medicine, Bristol-Myers Squibb, Samsung, AstraZeneca, Daiichi-Sankyo, Boerigher, GSK, Seattle Genetics, Guardant Health, Veracyte, Celcuity, Hengrui Therapeutics, Menarini, Merck, Exact Sciences, Blueprint Medicines, Gilead Sciences Speakers' Bureau: Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, Daiichi Sankyo, Seagen, Menarini, Gilead Sciences, Exact Sciences Research Funding: Merck Travel, Accommodations, Expenses: Roche/Genentech, Pfizer, Daiichi Sankyo, AstraZeneca      

Featuring a slide presentation and related discussion from Dr Laura Huppert, including the following topics: Overview of approved antibody-drug conjugates (ADCs) for metastatic hormone receptor-positive HER2-negative breast cancer — trastuzumab deruxtecan, sacituzumab govitecan and datopotamab deruxtecan(0:00) Approved and investigational ADCs for metastatic triple-negative breast cancer (17:18) Sequencing of ADCs for metastatic HER2-negative breast cancer; future research directions (26:10) CME information and select publications

How does a woman overcome her fear of needles to face a cancer diagnosis head-on? Valerie McDaniels' story of discovering a breast lump and delaying medical attention due to a phobia quickly escalates to a life-or-death struggle. A cruise in December 2023 revealed the critical nature of her condition when the mass burst, forcing her to seek urgent care. Ultimately, the support of her family and faith empowered Valerie to confront her fears and undergo necessary treatments. KEY QUESTIONS ANSWERED 1. Why did Valerie McDaniels conceal the breast lump from her husband? 2. What event triggered Valerie to finally seek medical help while on the cruise? 3. What was Valerie's initial reaction to her diagnosis, and why did she delay seeking treatment? 4. How did the medical staff on the cruise advise Valerie after she sought help for the bleeding ulcer? 5. What role did Valerie's primary care physician play in her treatment journey? 6. What was the significant outcome of Valerie's biopsy and mammogram at The Rose? 7. What methods did Valerie use to cope with her needle phobia during medical treatments? 8. Why did Valerie decide to undergo a double mastectomy, and what was the result? 9. How did Valerie's faith and support system impact her journey through cancer treatment? TIMESTAMPED OVERVIEW 00:00 Girl hides from doctor; last to leave. 03:53 Fear of needles causes anxiety, insomnia. 09:14 Called mom to hospital, bleeding profusely. 12:00 Doctor advises biopsy for suspected breast cancer. 12:51 Urgently went to the Rose for biopsy. 18:59 Stage 3 HER2-positive breast cancer diagnosis. 21:39 Struggled with starting treatment through port. 25:18 Relaxing helps; they're trying to help me. 27:42 Experience: Misunderstood sensations; sought clarity, shared feelings. 29:27 I regret causing my family unnecessary stress. 33:28 The Rose Galleria: Mammogram, ultrasound, biopsy services. Support The Rose HERE. Subscribe to Let’s Talk About Your Breasts on Apple Podcasts, Spotify, iHeart, and wherever you get your podcasts.See omnystudio.com/listener for privacy information.

Featuring case presentations and related discussion from Dr Sara A Hurvitz and Dr Sara M Tolaney, including the following topics: Case: A woman in her mid 50s with localized HR-negative, HER2-positive breast cancer — Dr Tolaney (0:00) Case: A woman in her mid 40s with localized HR-positive breast cancer with a germline BRCA2 mutation — Dr Tolaney (7:08) Case: A woman in her early 30s with HR-negative, HER2-positive metastatic breast cancer with one isolated liver metastasis — Dr Tolaney (11:30) Case: A woman in her early 50s with metastatic triple-negative breast cancer — Dr Tolaney (17:52) Case: A woman in her early 30s with localized HR-positive, HER2-negative breast cancer — Dr Hurvitz (31:49) Case: A woman in her early 60s with HR-positive, HER2-negative metastatic breast cancer with concurrent PIK3CA and ESR1 mutations — Dr Hurvitz (40:39) Case: A woman in her early 40s with recurrent HR-positive advanced breast cancer with a PIK3CA mutation — Dr Hurvitz (51:28) Case: A woman in her early 50s with HR-positive, HER2-negative breast cancer eligible for the SERENA-6 switching strategy — Angela DeMichele, MD, MSCE (58:41) CME information and select publications

“I think that this is an area that is exploding. Working with drug development, I see new agents all the time, with unique targets I've never heard about, with targets I have heard about used in a different way. So, I really think we're going to see more and more bispecifics. A lot of these drugs are used second line, third line, fourth line. I would not be surprised if they moved up in treatment, especially as we learn safer ways to give these drugs,” ONS member Moe Schwartz, PharmD, BCOP, FHOP, professor of pharmacy practice at the James L. Winkle College of Pharmacy at the University of Cincinnati, OH, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about bispecific antibodies.  Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by October 3, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learner will report an increase in knowledge related to the use of bispecific antibodies in the treatment of cancer. Episode Notes  Complete this evaluation for free NCPD. ONS Podcast™ episodes: Pharmacology 101 series Episode 275: Bispecific Monoclonal Antibodies in Hematologic Cancers and Solid Tumors Episode 261: CAR T-Cell Therapy for Hematologic Malignancies Requires Education and Navigation Episode 176: Oncologic Emergencies: Cytokine Release Syndrome ONS Voice articles: An Oncology Nurse's Guide to Bispecific Antibodies Bispecific Antibodies Cross-Discipline Cancer Care ONS Voice oncology drug reference sheets: Amivantamab-Vmjw Blinatumomab Epcoritamab-Bysp Glofitamab-Gxbm Mosunetuzumab-Axgb Tebentafusp-Tebn Teclistamab-Cqyv ONS book: Guide to Cancer Immunotherapy (second edition) ONS course: ONS/ONCC® Chemotherapy Immunotherapy Certificate™ Clinical Journal of Oncology Nursing article: Optimizing Transitions of Care in Multiple Myeloma Immunotherapy: Nurse Roles Other ONS resources: Bispecific Antibodies Video Bispecifics Huddle Card Cytokine Release Syndrome Huddle Card Immune Effector Cell–Associated Neurotoxicity Syndrome Huddle Card DailyMed homepage Hematology/Oncology Pharmacy Association late-breaking news article: The Emerging Use of Bispecific Antibodies with Chemotherapy in Diffuse Large B-Cell Lymphoma To discuss the information in this episode with other oncology nurses, visit the ONS communities.  To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org Highlights From This Episode “It was 2014 that most of us think of as the beginning of bispecifics in cancer, and that was with approval of blinatumomab. That was granted accelerated approval for the treatment of patients with Philadelphia chromosome–negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia. It is a bispecific that targets CD19-expressing tumor cells and CD3 on T cells. It's the original bispecific T-cell engager and is often called a ‘BiTE.'” TS 2:11 “The term ‘bispecific' means that this is an artificial protein that's developed to hit two different antigens simultaneously. They can be two different epitopes on the same antigen. They can be an antigen on a cancer cell and CD3 on a T cell that kind of recruits the T cell to the cancer. So, there are different types [of bispecific antibodies]. The subtype that we often talk about are bispecific T-cell engagers, which are those bispecifics that do target the T cell. And currently, the target on the T cell that's utilized is the CD3 molecule. That's not the only one that will be used in the future because there's a lot of work being done on other types of T-cell engagers.” TS 4:21 “The targets for lymphoma are CD20. Those are bispecific T-cell engagers that hit CD20 on the lymphoma cell, as well as CD3 on a T cell. ... In myeloma, we have two different targets that have been utilized. One is BCMA or B-cell maturation antigen. That sits on the surface of myeloma cells and on some healthy B cells. ... There's also a target used in myeloma that's called GPRC5D, which stands for G protein–coupled receptor, class C, group 5, member D. ... In small cell lung cancer, there's delta-like ligand 3 (DLL3); it's part of the NOTCH pathway. ... And then this year, we've had a couple agents come out that target HER2.” TS 6:52 “[Toxicities] are very dependent on what your target is. ... The bispecific T-cell engager that's used in myeloma that targets the GPRC5D is also expressed on tissues that produce hard keratin like hair follicles and actually, within the tongue. So the toxicities that we see with that agent are something you wouldn't expect to see if you were using a myeloma agent. You see nail and skin issues. You see taste problems. So it's very specific about the target, which says to me, that every time a new one of these agents comes out, I have to learn about the target that helps me learn about the toxicity. I find that fascinating and really appreciate that.” TS 16:19 “Cytokine release syndrome has been one of the areas that drug development has really focused on to see how they can help mitigate the severity [of it]. ... [One of] the strategies that has been incorporated and studied in clinical trials is the step-up dosing scheme. [It's] where you give initial small doses and over time, increase the dose to the dose you're going to continue with. Usually, monitoring in the hospital is required by the FDA approval for anywhere from 28–48 hours for the first couple of doses. And that's a real common strategy that you'll see. Premedication with H2 blockers, H1 blockers, sometimes steroids. These are also things that are incorporated within the approvals of these drugs and are important to look at.” TS 20:53