Podcasts about egfr

In this podcast, experts Tina Cascone, MD, PhD; Christina Baik, MD, MPH; and David Planchard, MD, PhD discuss data-driven treatment for EGFR-mutant non-small cell lung cancer.

Join us for another insightful episode of The Oncology Brothers as we dive into the Challenging Case Series! In this episode, we were joined by Dr. Eric Singhi, a thoracic medical oncologist from MD Anderson, to discuss the complexities of treating EGFR-positive non-small cell lung cancer (NSCLC). We explored the latest treatment options, including: •⁠  ⁠Osimertinib •⁠  ⁠Amivantamab plus Lazertinib (based on the MARIPOSA trial) •⁠  ⁠Osimertinib plus chemotherapy (from the FLAURA2 trial) Listen in as we analyze real-life patient cases, focusing on a 58-year-old gentleman with CNS involvement and a 66-year-old woman experiencing disease progression after initial treatment. Dr. Singhi shared valuable insights on the importance of supportive care, the impact of treatment combinations, and the significance of repeat tissue profiling. Key topics covered: •⁠  ⁠The latest data from the MARIPOSA and FLAURA2 trials •⁠  ⁠Strategies for managing side effects and improving patient quality of life •⁠  ⁠The role of multidisciplinary teams in treatment planning •⁠  ⁠The importance of understanding resistance patterns in treatment decisions Whether you're a healthcare professional or simply interested in oncology, this episode is packed with essential information and expert perspectives.  Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more episodes from The Oncology Brothers! #EGFRNSCLC #Mariposa #Amivantamab #Osimertinib #FLAURA2 #OncologyBrothers #LungCancer

Featuring an interview with Dr Aaron Lisberg, including the following topics: Efficacy and Safety of Datopotamab Deruxtecan (Dato-DXd) for Patients with Previously Treated EGFR-Mutated Advanced Non-Small Cell Lung Cancer (NSCLC): A Pooled Analysis of the TROPION-Lung01 and TROPION-Lung05 Trials (0:00) Ahn M-J et al. Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously-treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): A pooled analysis of TROPION-Lung01 and TROPION-Lung05. ESMO Asia 2024;Abstract LBA7 Ahn M-J et al. A pooled analysis of datopotamab deruxtecan in patients with EGFR-mutated NSCLC. J Thorac Oncol 2025;[Online ahead of print]. Abstract Sacituzumab Tirumotecan for Previously Treated Advanced EGFR-Mutated NSCLC: Results from the Randomized OptiTROP-Lung03 Study (7:08) Fang W et al. Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: Multicentre, open label, randomised controlled trial. BMJ 2025;389:e085680. Abstract Zhang L et al. Sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC): Results from the randomized OptiTROP-Lung03 study. ASCO 2025;Abstract 8507. Combination of Dato-DXd and Immunotherapy as First-Line Therapy for Patients with Advanced NSCLC (13:12) Cuppens K et al. First-line (1L) datopotamab deruxtecan (Dato-DXd) + durvalumab ± carboplatin in advanced or metastatic non-small cell lung cancer (a/mNSCLC): Results from TROPION-Lung04 (cohorts 2 and 4). ESMO Targeted Anticancer Therapies Congress 2025;Abstract 8O. Okamoto I et al. TROPION-Lung07: Phase III study of Dato-DXd + pembrolizumab ± platinum-based chemotherapy as 1L therapy for advanced non-small-cell lung cancer. Future Oncol 2024;20(37):2927-36. Abstract Levy BP et al. TROPION-Lung08: Phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC. Future Oncol 2023;19(21):1461-72. Abstract Aggarwal C et al. AVANZAR: Phase III study of datopotamab deruxtecan (Dato-DXd) + durvalumab + carboplatin as 1L treatment of advanced/mNSCLC. World Conference on Lung Cancer (WCLC) 2023;Abstract P2.04-02. TROP2-Targeting Antibody-Drug Conjugates as Neoadjuvant and/or Adjuvant Therapy for Patients with Resectable NSCLC (19:08) A phase III, randomised, open-label, global study of adjuvant datopotamab deruxtecan (Dato-DXd) in combination with rilvegostomig or rilvegostomig monotherapy versus standard of care, following complete tumour resection, in participants with Stage I adenocarcinoma non-small cell lung cancer who are ctDNA-positive or have high-risk pathological features (TROPION-Lung12). NCT06564844 Cascone T et al. Perioperative durvalumab plus chemotherapy plus new agents for resectable non-small-cell lung cancer: The platform phase 2 NeoCOAST-2 trial. Nat Med 2025;31(8):2788-96. Abstract CME information and select publications

En esta cápsula de ESMO 2025 EXPRESS, el Dr. Jerónimo Rodríguez Cid, oncólogo médico, jefe de oncología torácica del Instituto Nacional de Enfermedades Respiratorias en la Ciudad de México, nos comenta brevemente sobre los avances más relevantes en cáncer de pulmón. El experto comenta lo siguiente:Creo que el cambio más importante se está dando probablemente en el cáncer de pulmón de células pequeñas, donde ya contamos con dos estudios con resultados positivos. El primero evaluó tarlatamab en combinación con quimioinmunoterapia y mostró resultados favorables. El segundo combinó quimioterapia más inmunoterapia, seguida de mantenimiento con ceralasertib y durvalumab, también con desenlace positivo. Esto marca un avance relevante y alentador, especialmente para los pacientes con cáncer de pulmón de células pequeñas, que históricamente han tenido el pronóstico más desfavorable. En el cáncer de pulmón de células no pequeñas también se han observado avances significativos. Recientemente se publicaron los resultados de supervivencia libre de progresión a largo plazo del estudio con sevabertinib, junto con los datos positivos del estudio con zongertinib. Ambos ensayos mostraron resultados favorables.También se presentaron otros estudios relevantes. Entre ellos, el FLAURA 2, del que ya conocíamos el beneficio en supervivencia global y supervivencia libre de progresión en pacientes con mutaciones EGFR tratados con osimertinib más quimioterapia. En esta ocasión se mostró un subanálisis en pacientes de mal pronóstico, donde con excepción de aquellos con alteración en P53 la mayoría continuó beneficiándose del tratamiento, lo cual es un hallazgo importante.Además, se actualizó el estudio PHAROS, que evalúa la combinación de encorafenib + binimetinib en pacientes con mutación BRAF positiva. Los resultados confirmaron una excelente supervivencia libre de progresión y una supervivencia global que alcanza hasta los cuatro años, consolidando esta combinación como una opción potencialmente estándar para este grupo de pacientes.También se presentaron datos interesantes sobre terapias dirigidas. Por un lado, lorlatinib demostró capacidad para superar las resistencias a crizotinib en pacientes ROS1 positivos cuando se utiliza como tratamiento de segunda línea. Por otro, el brigatinib, administrado después de alectinib en pacientes ALK positivos, mostró resultados positivos, destacando como una alternativa eficaz en esta secuencia terapéutica.Entre otros temas.Material exclusivo para profesionales de la salud. Este material ha sido desarrollado únicamente con fines educativos e informativos y no tiene la intención de sustituir el juicio clínico de los profesionales de la salud. Las opiniones y declaraciones presentadas en este contenido son responsabilidad exclusiva de los ponentes y no reflejan necesariamente la postura institucional de ScienceLink ni de terceros mencionados. La información presentada se basa en el conocimiento y la experiencia profesional de los ponentes. La veracidad, exactitud y actualidad científica de los datos son de su exclusiva responsabilidad. Así mismo garantizan que el contenido utilizado no infringe derechos de autor de terceros y asumen toda responsabilidad por su uso. Se deberán de revisar las indicaciones aprobadas en el país con estricto apego al marco regulatorio aplicable para cada uno de los tratamientos y medicamentos comentados. ESMO® es una marca registrada de la European Society For Medical Oncology. Este material ha sido producido de manera independiente y no está autorizado, patrocinado ni avalado por dicha organización.

En esta cápsula de ESMO 2025 EXPRESS, la Dra. Tannia Soria, oncóloga clínica adscrita al Hospital de Solca en Quito, Ecuador nos comenta brevemente sobre los avances más relevantes en cáncer de pulmón.La experta comenta lo siguiente: Se ha visto en los resultados finales de sobrevida global, como en el estudio FLAURA2, que la incorporación de quimioterapia basada en platino y pemetrexed al tratamiento con osimertinib mejoró de forma significativa y clínicamente relevante la sobrevida global.Este estudio con el tiempo nos permitirá contar en el contexto de pacientes con cáncer de pulmón de células no pequeñas con mutación de EGFR con tres alternativas terapéuticas que ayudarán a perfilar mejor a cada paciente. Tendremos la opción de monoterapia, así como combinaciones como las evaluadas en los estudios FLAURA2 y MARIPOSA, que en conjunto ampliarán nuestras posibilidades para seleccionar el tratamiento más adecuado.También vale la pena mencionar el estudio NORTHSTAR, que resultó particularmente interesante, ya que demostró que la incorporación de una terapia local ablativa o de consolidación puede mejorar los resultados cuando se combina con osimertinib, incrementando la sobrevida libre de progresión y reduciendo de manera significativa el riesgo de progresión.Asimismo, otro trabajo relevante en cáncer de pulmón es el estudio ALEX, cuyos resultados finales de sobrevida mostraron que, en comparación con crizotinib, se logró una mejora sustancial en la sobrevida global, especialmente en pacientes con factores de alto riesgo, como metástasis cerebrales, hepáticas o presencia de mutación en P53.Fecha de grabación: 19 de octubre de 2025Material exclusivo para profesionales de la salud. Este material ha sido desarrollado únicamente con fines educativos e informativos y no tiene la intención de sustituir el juicio clínico de los profesionales de la salud. Las opiniones y declaraciones presentadas en este contenido son responsabilidad exclusiva de los ponentes y no reflejan necesariamente la postura institucional de ScienceLink ni de terceros mencionados. La información presentada se basa en el conocimiento y la experiencia profesional de los ponentes. La veracidad, exactitud y actualidad científica de los datos son de su exclusiva responsabilidad. Así mismo garantizan que el contenido utilizado no infringe derechos de autor de terceros y asumen toda responsabilidad por su uso. Se deberán de revisar las indicaciones aprobadas en el país con estricto apego al marco regulatorio aplicable para cada uno de los tratamientos y medicamentos comentados. ESMO® es una marca registrada de la European Society For Medical Oncology. Este material ha sido producido de manera independiente y no está autorizado, patrocinado ni avalado por dicha organización.

En esta cápsula de ESMO 2025 EXPRESS, el Dr. Mariano Dioca, oncólogo médico adscrito al Instituto de Oncología Ángel H. Roffo en Buenos Aires, Argentina, nos habla sobre las principales novedades en tumores gastrointestinales, destacando cuatro estudiosrelevantes:El estudio PHERFLOT (fase II) evaluó pembrolizumab y trastuzumab en combinación con FLOT frente FLOT en pacientes HER2-positivos con cáncer gástrico o de la unión esofagogástrica. El PERISCOPE II (fase III) analizó la citorreducción peritoneal más HIPEC en cáncer gástrico avanzado, sin demostrar beneficio en supervivencia global.El CITRIC (fase II) exploró el retratamiento con cetuximab + irinotecán frente a terapia estándar (sin inhibidores de EGFR). Finalmente, el PARERE (fase II) comparó las secuencias panitumumab-regorafenib versus regorafenib-panitumumab en el contexto de rechallenge anti-EGFR. 4En conjunto, estos estudios aportan evidencia relevante sobre el papel del rechallenge anti-EGFR y las estrategias inmuno-quimioterápicas en cáncer gástrico y colorrectal avanzado. Referencias:Pembrolizumab and trastuzumab in combination with FLOT in the perioperative treatment of HER2-positive localized esophagogastric adenocarcinoma: Interim analysis of the phase II PHERFLOT/IKF-053 trial of the AIO study group (AIO STO 0321). Abstract # 2095MO, presentado en el marco del Congreso Anual de la Sociedad Europea de Oncología Médica (ESMO®) 2025, celebrado del 17 al 21 de octubre de 2025 en Berlín, Alemania.Systemic therapy, gastrectomy and CRS/HIPEC vs systemic therapy alone for gastric cancer with limited peritoneal dissemination: Results of the randomised PERISCOPE II trial. Abstract #2096MO, presentado en el marco del Congreso Anual de la Sociedad Europea de Oncología Médica (ESMO®) 2025, celebrado del 17 al 21 de octubre de 2025 en Berlín, Alemania.Circulating tumor (ct) DNA-guided anti-EGFR rechallenge strategy in metastatic colorectal cancer (mCRC): Final results of the phase II randomized CITRIC trial. Abstract #LBA33, presentado en el marco del Congreso Anual de la Sociedad Europea de Oncología Médica (ESMO®) 2025, celebrado del 17 al 21 de octubre de 2025 en Berlín, Alemania.Panitumumab retreatment followed by regorafenib versus the reverse sequence in chemorefractory metastatic colorectal cancer patients with RAS and BRAF wild-type circulating tumor DNA (ctDNA): Final results of the randomized PARERE trial by GONO. Abstract #LBA32, presentado en el marco del Congreso Anual de la Sociedad Europea de Oncología Médica (ESMO®) 2025, celebrado del 17 al 21 de octubre de 2025 en Berlín, Alemania.Fecha de grabación: 18 de octubre de 2025 Material exclusivo para profesionales de la salud. Estematerial ha sido desarrollado únicamente con fines educativos e informativos y no tiene la intención de sustituir el juicio clínico de los profesionales de la salud. Las opiniones y declaraciones presentadas en este contenido son responsabilidad exclusiva de los ponentes y no reflejan necesariamente la postura institucional de ScienceLink ni de terceros mencionados. La información presentada se basa en el conocimiento y la experiencia profesional de los ponentes. La veracidad, exactitud y actualidad científica de los datos son de su exclusiva responsabilidad. Así mismo garantizan que el contenido utilizado no infringe derechos de autor de terceros y asumen toda responsabilidad por su uso. Se deberán de revisar las indicaciones aprobadas en el país con estricto apego al marco regulatorio aplicable para cada uno de los tratamientos y medicamentos comentados.  ESMO® es una marca registrada de la European Society ForMedical Oncology. Este material ha sido producido de manera independiente y no está autorizado, patrocinado ni avalado por dicha organización.

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 today's episode, leading experts across oncology specialties previewed the key studies and data they are most anticipating ahead of the 2025 ESMO Congress. Dana M. Chase, MD, a professor of Clinical Obstetrics and Gynecology in the Division of Gynecologic Oncology at UCLA, discussed her excitement to see findings from a phase 1 trial (NCT05403554) investigating NI-1801 in patients with heavily pretreated, mesothelin-expressing platinum-resistant epithelial ovarian cancer. Premal H. Thaker, MD, MS, the David G. and Lynn Mutch Distinguished Professor of Obstetrics and Gynecology and director of Gynecologic Oncology Clinical Research at Siteman Cancer Center in Saint Louis, Missouri, discussed the anticipation for findings from a multi-omic analysis of the phase 3 AtTEnd/ENGOT-EN7 trial (NCT03603184) of atezolizumab in patients with endometrial cancer and data demonstrating that the WES-derived Aneuploidy Score may identify patients with mismatch repair–deficient endometrial cancer who derive reduced benefit from immunotherapy. Zev Wainberg, MD, the Estelle, Abe, and Marjorie Sanders Chair in Cancer Research at UCLA, shared his anticipation for new data in gastrointestinal oncology, particularly the overall survival results from the phase 3 MATTERHORN trial (NCT04592913) of durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel in patients with resectable gastric and gastroesophageal cancer, which are expected to provide pivotal updates following previously reported event-free survival outcomes. Sagus Sampath, MD, an associate clinical professor and medical director of the Department of Radiation Oncology at City of Hope in Duarte, California, highlighted the phase 2 NorthStar trial (NCT03410043) evaluating osimertinib (Tagrisso) with or without local consolidative therapy in patients with metastatic EGFR-mutated non–small cell lung cancer (NSCLC).

The Phase 2b COPERNICUS Study of Subcutaneous Amivantamab with Lazertinib as First-Line Treatment, or with Chemotherapy as Second-Line Treatment, for EGFR-Mutated Non-Small Cell Lung Cancer: a Vodcast Dr. Balazs Halmos and Dr. Melissa Johnson present the phase 2b COPERNICUS study evaluating subcutaneous amivantamab, with lazertinib as first-line treatment, or with chemotherapy as second-line treatment for EGFR-mutated non-small cell lung cancer.The intent of this vodcast is to review the study design for COPERNICUS, highlighting how it combines pragmatic elements to assess the efficacy and safety of subcutaneous amivantamab with supportive care for prevention and management of adverse events in a diverse participant population. This vodcast is published open access in Oncology and Therapy and is fully citeable. You can access the original published podcast article through the Oncology and Therapy website and by using this link: https://link.springer.com/article/10.1007/s40487-025-00386-8. All conflicts of interest can be found online. This podcast is intended for medical professionals. Open Access This podcast is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The material in this podcast is included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

JCO PO author Dr. Asaf Maoz at Dana-Farber Cancer Institute shares insights into article, “Causes of Death Among Individuals with Lynch Syndrome in the Immunotherapy Era.” Host Dr. Rafeh Naqash and Dr. Maoz discuss the causes of death in individuals with LS and the evolving role of immunotherapy. 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 JCOPO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Associate Professor Medicine, at the OU Health Stephenson Cancer Center. Today, I'm super thrilled to be joined by Dr. Asaf Maoz, Medical Oncologist at Dana-Farber Cancer Institute, Brigham and Women's Hospital, and faculty at the Harvard Medical School, and also lead author on the JCO Precision Oncology article entitled "Causes of Death Among Individuals with Lynch Syndrome in the Immunotherapy Era." This publication will be a concurrent publication with an oral presentation at the annual CGA meeting. At the time of this recording, our guest's disclosures will be linked in the transcript. Asaf, I'm excited to welcome you on this podcast. Thank you for joining us today. Dr. Asaf Maoz: Thank you so much for highlighting our paper. Dr. Rafeh Naqash: Absolutely. And I was just talking to you that we met several years back when you were a trainee, and it looks like you've worked a lot in this field now, and it's very exciting to see that you consider JCOPO as a relevant home for some of your work. And the topic that you have published on is of significant interest to trainees from a precision medicine standpoint, to oncologists in general, covers a lot of aspects of immunotherapy. So, I'm really excited to talk to you about all of this. Dr. Asaf Maoz: Me too, me too. And yeah, I think JCOPO has great content in the area of cancer genetics and has done a lot to disseminate the knowledge in that area. Dr. Rafeh Naqash: Wonderful. So, let's get started and start off, given that we have hosts of different kinds of individuals who listen to this podcast, especially when driving from home to work or back, for the sake of making everything simple, can we start by asking you what is Lynch syndrome? How is it diagnosed? What are some of the main things to consider when you're trying to talk an individual where you suspect Lynch syndrome? Dr. Asaf Maoz: Lynch syndrome is an inherited predisposition to cancer, and it is common. So, we used to think that, or there's a general notion in the medical community that it is a rare condition, but we actually know now from multiple studies, including studies that look at the general population and do genetic testing regardless of any clinical phenotype, that Lynch syndrome is found in about 1 in 300 people in the general population. If you think about it in the United States, that means that there are over a million people living with Lynch syndrome in the United States. Unfortunately, most individuals with Lynch syndrome don't know they have Lynch syndrome at the current time, and that's where a lot of the efforts in the community are being made to help detect more individuals who have Lynch syndrome. Lynch syndrome is caused by pathogenic germline variants in mismatch repair genes, MLH1, MSH2, MSH6, or PMS2, or as a result of pathogenic variants in EPCAM that cause silencing of the MSH2 gene. Dr. Rafeh Naqash: Excellent. Thank you for that explanation. Now, one of the other things I also realized, similar to BRCA germline mutations, where you require a second hit for individuals with Lynch syndrome to have mismatch repair deficient cancers, you also require a second hit to have that second hit result in an MSI-high cancer. Could you help us understand the difference of these two concepts where generally Lynch syndrome is thought of to be cancers that are mismatch repair deficient, but that's not necessarily true for all cases as we see in your paper. Can you tease this out for us a little bit more? Dr. Asaf Maoz: Of course, of course. So, the germline defect is in one of the mismatch repair genes, and these genes are responsible for DNA mismatch repair, as their name implies. Now, in a normal cell, we think that one working copy is generally enough to maintain the mismatch repair machinery intact. What happens in tumors, as you alluded to, is that there is a second hit in the same mismatch repair gene that has the pathogenic germline variant, and that causes the mismatch repair machinery not to work anymore. And so what happens is that there is formation of mutations in the cancer cell that are not present in other cells in the body. And we know that there are specific types of mutations that are associated with defects in mismatch repair mechanisms, and those are associated a lot of times with frameshift mutations. And we have termed them ‘microsatellites'. So there are areas in the genome that have repeats, for example, you know, if you have AAAA or GAGA, and those areas are particularly susceptible to mutations when the mismatch repair machinery is not working. And so we can measure that with DNA microsatellite instability testing. But we can also get a sense of whether the mismatch repair machinery is functioning by looking at protein expression on the surface of cancer cells and by doing immunohistochemistry. More recently, we're also able to infer whether the mismatch repair machinery is working by doing next-generation sequencing and looking at many, many microsatellites and whether they have this DNA instability in the microsatellites. Dr. Rafeh Naqash: Excellent explanation. As a segue to what you just mentioned, and this reminds me of some work that one of my good friends, collaborators, Amin Nassar, whom you also know, I believe, had done a year and a half back, was published in Cancer Cell as a brief report, I believe, where the concept was that when you look at these mismatch repair deficient cancers, there is a difference between NGS testing, IHC testing, and maybe to some extent, PCR testing, where you can have discordances. Have you seen that in your clinical experience? What are some of your thoughts there? And if a trainee were to ask, what would be the gold standard to test individuals where you suspect mismatch repair deficient-related Lynch syndrome cancers? How would you test those individuals? Dr. Asaf Maoz: We do sometimes see discordance, you know, from large series, the concordance rate is very high, and in most series it's over 95%. And so from a practical perspective, if we're thinking about the recommendation to screen all colorectal cancer and all endometrial cancer for mismatch repair deficiency, I think either PCR-based testing or immunohistochemistry is acceptable because the concordance rate is very high. There are rare cases where it is not concordant, doing multiple of the tests makes sense at that time. If you think about the difference between the tests, the immunohistochemistry looks at protein expression, which is a surrogate for whether there is mismatch repair deficiency or not, right? Because ultimately, the mismatch repair deficiency is manifested in the mutations. So if the PCR does not show microsatellite instability and now NGS does not show microsatellite instability, the IHC may be a false positive. At the end of the day, the functional analysis of whether there are actually unstable microsatellites either by PCR or by NGS is what I would consider more informative. But IHC again is an excellent test and concordant with those results in over 95% of cases. Now there is also an issue of sampling. It's possible that there's heterogeneity within the tumor. We published a case in JCOPO about heterogeneity of the mismatch repair status, and that was both by immunohistochemistry, but also by PCR. So there are some caveats and interpreting these tests does require some expertise, and I'm always happy to chat with trainees or whoever has an interesting or challenging case. Dr. Rafeh Naqash: Thanks again for that very easy to understand explanation. Now going to management strategies, could you elaborate a little bit upon the neo-adjuvant data currently, or the metastatic data which I think more people are familiar with for immunotherapy in individuals with MSI-high cancers? Dr. Asaf Maoz: Yeah, that's an excellent question and obviously a very broad topic. Individuals with Lynch syndrome typically develop tumors that are mismatch repair deficient or microsatellite unstable. And we have seen over the last 15 years or so that these tumors, because they have a lot of mutations and because these mutations are very immunogenic, we have seen that they respond very well to immunotherapy. And this has been shown across disease sites and has been shown across disease settings. And for that reason, immunotherapy was approved for MSI-high or mismatch repair deficient cancer regardless of the anatomic site. It was the first tissue-agnostic approval by the FDA in 2017. And so there are exciting studies both in the metastatic setting where we see individuals who respond to immunotherapy for many years, and one could wonder whether their cancer is going to come back or not. And also in the earlier setting, for example, the Cercek et al. study in the New England Journal from Sloan Kettering, where they showed that neoadjuvant immunotherapy can cause durable responses for rectal cancer that is mismatch repair deficient. And in that series, the patients did not require surgery or radiation, which is standard of care for rectal cancer otherwise. And there's also exciting data in the adjuvant space, as was presented in ASCO by Dr. Sinicrope, the ATOMIC study, and many more efforts to bring immunotherapy into the treatment landscape for individuals with MSI-high cancer, including individuals with Lynch syndrome. Dr. Rafeh Naqash: A lot of activity, especially in the neo-adjuvant and adjuvant space over the last two years or so. Now going to the actual reason why we are here is your study. Could you tell us why you looked at this idea of patients who had Lynch syndrome and died, and the reasons for their death? What was the thought that triggered this project? Dr. Asaf Maoz: As we were talking about, we now know that immunotherapy really has changed the treatment landscape for individuals with Lynch syndrome, and that most cancers that individuals with Lynch syndrome do have this mismatch repair deficiency. But we also know that individuals with Lynch syndrome can develop tumors that do not have mismatch repair deficiency, and we call them mismatch repair proficient or microsatellite stable. And there was a series from Memorial Sloan Kettering showing that in colorectal cancer, about 10% of the tumors that individuals with Lynch syndrome developed did not have mismatch repair deficiency. In addition to that, we anecdotally saw that some of our patients with Lynch syndrome died of causes that were not mismatch repair deficient tumors. We wanted to see how that has changed since immunotherapy was approved in a tissue-agnostic manner, meaning that we could look at this regardless of where the cancer started, because we would anticipate that if the tumor was mismatch repair deficient, the patient would be able to access immunotherapy as standard of care. Dr. Rafeh Naqash: Thank you. And then you looked at different aspects of correlations with regards to individuals that had an MSI-high cancer with Lynch syndrome or an MSS cancer with Lynch syndrome. Could you elaborate on some of the important findings that you identified as well as some of the unusual findings that perhaps we did not know about, even though the sample size is limited, but what were some of the unique things that you did identify through this project? Dr. Asaf Maoz: The first question was what cause is leading to death in individuals with Lynch syndrome? And we had 54 patients that we identified that had died since the approval of immunotherapy in 2017, 44 of which died of cancer-related causes. And when we looked at cancer-related causes of death, we wanted to know how many of those were due to mismatch repair deficient tumors versus mismatch repair proficient tumors or MS-stable tumors. And we found, somewhat surprisingly, that 43% of patients in our cohort actually died of tumors that were microsatellite stable or mismatch repair proficient, meaning of tumors that are not typically associated with Lynch syndrome. This is not entirely surprising as a cause of death because we know that immunotherapy does not typically work for tumors that are microsatellite stable. And so in the metastatic setting, there are much less cases of durable remissions with treatment. But it was helpful to have that figure as an important benchmark. There are previous studies about causes of death in Lynch syndrome, and particularly from the Prospective Lynch Syndrome Database in Europe. Those have provided really important information about cause of death by cancer site, but they typically don't have mismatch repair status and are more difficult to interpret in that regard. They also don't include a large number of individuals who have PMS2 Lynch syndrome, which is the most common, but least penetrant form of Lynch syndrome. Dr. Rafeh Naqash: As far as the subtype of pathogenic germline variants is concerned, did you notice anything unusual? And I've always had this question, and you may know more about this data, is: In the bigger context of immunotherapy, does the type of the pathogenic germline variant for Lynch syndrome associated MSI-high cancers, does that impact or have an association with the kind of outcomes, how soon a cancer progresses or how many exceptional responders perhaps with MSI-high cancers actually have a certain specific pathogenic germline variant? Dr. Asaf Maoz: That's an excellent question, and certainly we need more data in that space. We know that the type of germline mutation, or the gene in which there is a germline pathogenic variant, determines to a large degree the cancer risk, right? So we know that individuals who have germline pathogenic variants in MLH1 or MSH2 have a much higher colorectal cancer risk than, for example, PMS2. We know that for PMS2, the risks are more limited to colorectal and endometrial, and may be lower risk of other cancers. We also know that, you know, the spectrum of disease may change based on the pathogenic germline variants. For example, individuals who have MSH2 associated Lynch syndrome have more risk of additional cancers in other organs like the urinary tract and other less common Lynch-associated tumors. The question about response to therapy is one where we have much less information. There are studies that are trying to assess this, but I don't think the answer is there yet. Some of the non-clinical data looks at how many mutations there are based on the pathogenic variant and what the nature of those mutations are, whether they're more frameshift or others. But I think we still need more clinical data to understand whether the response to immunotherapy differs. It's also complicated by the fact that the immunotherapy landscape is changing, especially in the metastatic setting, now with the approval of combination ipilimumab and nivolumab for first-line treatment of colorectal cancer that is microsatellite unstable. But in our study, we did find that, as you would expect, there is an enrichment in MS-stable cancers among those with PMS2 Lynch syndrome. Again, our denominator is those who died, right? So this is not the best way to look at the question whether this is overall true, that is more addressed by the study that Sloan Kettering published. But we do see, as we would anticipate, that there are more microsatellite stable cancers among those with PMS2 Lynch syndrome that died. Dr. Rafeh Naqash: A lot to uncover there for sure. This study and perhaps some of the other work that you're doing is slowly advancing our understanding of some of these concepts. So I'd like to shift gears to a couple of provocative questions that I generally like to ask. The first is, in your opinion, and you may or may not have data to back this up, which is okay, and that's why we're having a conversation about it. In your opinion, do you think the type or the quality of the neoantigen is different based on the pathogenic germline variant and a Lynch syndrome associated MSI-high cancer? Dr. Asaf Maoz: I think there are some data out there that, you know, I can't cite off the top of my mind, but there are some data out there that suggest that that may be the case. I think the key question is the quality, right? I think that whether these differences that are found on a molecular level also translate to a clinical difference in response is something that is unknown at this moment. Some people hypothesize that if the tumor has less neoantigens, there's less of a response to immunotherapy. But I think we really need to be careful before making those assertions on a clinical level. I do think it's a really important question that needs to be answered, among others because, you know, in the colorectal space, for example, where we have both the option of doing ipilimumab with nivolumab and the option of doing pembrolizumab, we don't really know which patients need the CTLA-4 blockade versus which patients can receive PD-1 blockade alone and avoid the potential excess toxicity of the CTLA-4 blockade. There are a lot of interesting questions there that still need to be answered. And of course, individuals with Lynch syndrome are just a fraction of those individuals who have MSI-high cancer. So there's also the question about whether non-Lynch syndrome associated MSI-high cancer responds differently to immunotherapy than Lynch syndrome associated MSI-high cancer. A lot of very interesting questions in the field for sure. Dr. Rafeh Naqash: Absolutely. My second question is more about trying to understand the role of ctDNA, MRD monitoring in individuals with Lynch syndrome. If somebody has a germline, you know, Lynch syndrome MSI-high cancer, when you do a tumor-informed ctDNA assessment, what do you capture generally there? Because, and this question stems from a discussion I've had with somebody regarding EGFR lung cancer, since I treat individuals with lung cancer, and the concept generally is that even if the tissue showed EGFR, but for MRD monitoring, when you do a barcoded sequence of different tumor specific mutations, it's not actually the EGFR that they track in the blood when they do ctDNA assessment. But from a Lynch syndrome standpoint, if you have a germline, right, which is the first hit, and then you have the somatic in the tumor, which is the second hit, are you aware or have you tried to look into this where what is exactly being followed if one had to follow MRD in a Lynch syndrome MSI-high colorectal cancer? Dr. Asaf Maoz: I think a lot of the MRD assays are proprietary, and so we don't receive information about what the mutations that are being tracked are. In general, the idea is to track mutations that we would not expect to disappear as part of resistant mechanisms. We want these to be truncal mutations. We want these to be mutations in which resistance is not expected to result in reversion mutations. But what specifically is being tracked is something that I don't know because these assays, the tumor-informed ones, are proprietary, and we don't get the results regarding specific mutations. When it's circulating tumor DNA that is not necessarily tumor-informed, we do get those results, but that is less so about the specific selection of mutations. Dr. Rafeh Naqash: Thank you for clarifying that question to some extent, of course, as you said, we don't know a lot, and we don't know what we don't know. That's the most important thing that I've learned in the process of understanding precision medicine and genomics, and it's a very fast-paced evolving field. Last question related to your project, what is the next step? Are you planning any next steps as a bigger multicenter study or validation of some sort? Dr. Asaf Maoz: There are two big questions that this study raises. One, is this true across multiple other sites, right? Because this is a single center study, and we really need additional centers to look at their data and validate whether they are also seeing that a substantial portion of deaths in individuals with Lynch syndrome are attributable to mismatch repair proficient cancer. The other question is whether we can look at specifically MSI-high cancer versus MS-stable cancer and understand what the mortality rate for each of those are. From a clinical perspective, it's important to counsel individuals with Lynch syndrome about general cancer screening outside of mismatch repair deficient tumors and to understand that there is also a risk of mismatch repair proficient tumors and that treatment for those tumors would be different. There's a lot of work to be done in the future. Another major area of need is to see whether tumors that are microsatellite stable can be sensitized to immunotherapy, and that is beyond the Lynch syndrome field, but that is something that certainly would benefit these individuals with Lynch syndrome who develop mismatch repair proficient cancer. Dr. Rafeh Naqash: That's very interesting to hear, and we'll look forward to seeing some of those developments shape in the next few years. Now, I'd like to spend a minute, minute and a half on you specifically as a researcher, clinician, scientist. Could you briefly highlight - because I remember meeting you several years back as a trainee, with your interest in genomics, computational research - could you briefly tell us what led you to hereditary cancer syndromes based on your research and work? What are some of the things that you learned along the way that other early career investigators can perhaps take lessons from? Dr. Asaf Maoz: Big questions there, thanks for asking. I got interested in the field of hereditary cancer syndromes when I came to the United States and started doing lab research in Stephen Gruber's lab at the time at USC. He's now at City of Hope. And my interest was originally looking at immunotherapy and immunology, but I went to the case conferences where we were learning about individuals with hereditary cancer, and those were kind of earlier days where we were still trying to figure out how to test and what the implications for these individuals would be. And through fellowship, I was also very interested in that, and I did my senior fellowship years with Dr. Yurgelun here at Dana-Farber, who is the director of the Lynch Syndrome Center. And I I think it's the combination between being able to treat individuals based on precision medicine and what the germline mutation is, but also the ability to prevent cancer and to develop strategies to intercept cancer early that is really appealing to me in this field. It's also a great field to be in because it's a small field. If you come to the CGA-IGC meeting, you'll be able to interact with everyone. Everyone is super collaborative, super nice, and I really recommend it to trainees. The CGA-IGC annual meeting is really a great opportunity to learn more and experience some of the advancement specifically in the GI hereditary space. Lessons for trainees. I think there are a lot of lessons that I could think about, but I think finding strong and supportive mentors is one of the things that has helped me most. I think that just having close relationship with your mentor, having frequent discussions and honest discussions about what is feasible, what is going to make a difference for your patients and your research and what you want to focus on is really important. And so I think if I had to choose one thing, I would say choose a mentor that you trust, that you feel you have a good relationship with, and that has the availability to support you. Dr. Rafeh Naqash: Thank you so much for those insightful comments, and thank you for sharing with us your journey, your project, and some of your interesting thoughts on this concept of hereditary cancers. Hopefully, we'll see more of this work being published in JCOPO through your lab or work from others. Dr. Asaf Maoz: Thank you so much. I appreciate the opportunity to be here. 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 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.

In today's episode, we had the pleasure of speaking with Lyudmila Bazhenova, MD, about the FDA approval of sunvozertinib (Zegfrovy) for patients with EGFR-mutated metastatic non–small cell lung cancer (NSCLC). Dr Bazhenova is a clinical professor of medicine at the University of California San Diego (UCSD); as well as a medical oncologist at the UCSD Moores Cancer Center. In our exclusive interview, Dr Bazhenova discussed the significance of this approval, key efficacy and safety data from the pivotal the phase 1/2 WU-KONG1B trial (NCT03974022), and how the use of sunvozertinib in the NSCLC treatment paradigm may propel future possibilities for the use of EGFR-directed agents in this disease.

Lung Cancer Considered: Targeting EGFR NSCLC by IASLC

As part of IASLC's ongoing series of Lung Cancer Considered podcasts in world languages, Dr. Lizza Hendriks moderates a discussion in Dutch with Dr. Marthe Paats and Dr. Gerrina Ruiter on the treatment of EGFR non-small cell lung cancer.

In this episode, we explore the evolving role of surrogate endpoints in the management of IgA nephropathy (IgAN), with a particular focus on the significance of estimated glomerular filtration rate (eGFR). Of the completed Phase 3 trials in IgAN, one used time-weighted average eGFR, an area under the curve-based measure that reflects the average change in eGFR from baseline over a specified period, in this case, over the full 2-year study period. The other trial used total eGFR slope to describe the overall rate of change over 2 years. But what do these endpoints mean outside the setting of a clinical trial? Expert insights shed light on how proteinuria and eGFR trends can inform prognosis and guide treatment decisions in clinical practice over the long term. Listeners will gain a deeper understanding of how to interpret eGFR changes over time and apply this knowledge to optimize patient care. Designed for nephrology professionals, this episode offers practical, evidence-based perspectives on integrating these surrogate endpoints into the care of patients with IgAN. Supported by Calliditas Therapeutics Upon completion of the podcast, please take a moment to complete a brief survey: https://kidneyforms.tfaforms.net/4728109

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

The first growth factors identified and studied during the early 1970s were Epidermal Growth Factor (EGF) and Nerve Growth Factor (NGF). It was soon demonstrated that EGF and NGF mediate their cellular and physiological effects by binding to specific cell membrane receptors: the EGF receptor (EGFR) and the NGF receptor (NGFR), respectively. The mechanisms of activation and signaling of these receptors were compared to those of insulin and IGF1, which bind and activate the Insulin Receptor (IR) and IGF1 Receptor (IGF1R). These comparisons gained further significance with the discovery that EGFR, NGFR, IR, IGF1R, and many other membrane receptors belong to the receptor tyrosine kinase (RTK) family of cell signaling molecules. Early insights into the activation and signaling mechanisms of EGFR revealed that ligand binding to its extracellular domain induces and stabilizes the formation of EGFR dimers. This dimerization plays a critical role in activating the receptor's intrinsic tyrosine kinase activity. Through an intermolecular process, this activation leads to the autophosphorylation of multiple tyrosine residues in the C-terminal tail of EGFR. The cytoplasmic domain of EGFR serves not only as an enzyme that phosphorylates various substrates but also as a scaffold that recruits and regulates multiple signaling proteins through complex formation. While different ligands induce RTK dimerization and activation through variations on a shared theme, this paradigm is universal among all RTKs and is similarly observed in the activation of other surface receptors. Further important discoveries regarding the mode of action of EGFR and other RTKs made during the 1970s and 1980s include the following: Signaling Modules: Molecules containing SH2, SH3, and other small protein modules were found to play key roles in mediating cellular activities downstream of RTKs and many other signaling molecules. Ligand-Dependent Endocytosis: Ligand binding to the extracellular domain of RTKs stimulates receptor-mediated endocytosis and intracellular trafficking ,which are essential for proper signal transduction. Oncogenic Mutations: A variety of gain-of-function oncogenic mutations were identified in EGFR and other RTKs. These mutations were shown to be critical drivers of many human cancers. These early discoveries, along with others made during the 1980s, laid the conceptual groundwork for the development of targeted therapies. They paved the way for the discovery and clinical application of more than 50 targeted small-molecule cancer drugs and therapeutic antibodies, which have significantly improved patient outcomes in oncology.

In this episode, Dr. Paul Wheatley-Price is back for another update into all the newest highlights from recent clinical trials for EGFR-positive lung cancer treatments. Dr. Stephen Liu is the Director of Thoracic Oncology and Professor of Medicine at Georgetown University in Washington, DC, and he co-hosts his own podcast with the IASLC, "Lung Cancer Considered". They are also joined by Emi Bossio, a passionate patient advocate who lives with EGFR+ lung cancer and has a number of roles, including as a member on LCC's Board of Directors.

The OncoAlert Weekly Roundup is your go-to podcast for the latest, most impactful updates in oncology from across the globe

Join us in this episode of the Oncology Brothers podcast as we dive into the highlights from the World Conference on Lung Cancer 2025! We are joined by Dr. Balazs Halmos, a thoracic medical oncologist at the Montefiore Einstein Cancer Center, to discuss three pivotal studies that are shaping the future of lung cancer treatment. In this episode, we covered: •⁠  ⁠FLAURA2 Trial: Discover the significant overall survival benefits of combining osimertinib with chemotherapy for patients with EGFR-positive non-small cell lung cancer, and how it compares to single-agent osimertinib. •⁠  ⁠HARMONi Trial: Explore the intriguing yet complex findings of a new bi-specific antibody targeting PD-1 and VEGF in patients with progressive EGFR-mutated disease, and the implications of its current negative results. •⁠  ⁠ALCHEMIST Trial: Learn about the role of crizotinib in the adjuvant setting for ALK-positive lung cancer and why it reinforces alectinib as the standard of care. Tune in for an insightful discussion on the latest advancements in precision medicine, the importance of ctDNA, and the evolving landscape of lung cancer treatment.  Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers!

Today, I'm joined by the remarkable Dr. Robin Rose—a pioneering physician, author, and survivor who refused to accept a devastating kidney disease diagnosis as her fate. Instead of waiting for dialysis, Robin dove deep into the world of diet, detoxification, peptides, and bioregulators, turning her health crisis into a calling and culminating in her groundbreaking new book on chronic kidney disease. In our conversation, Robin shares why kidneys are often the “forgotten organ,” the real reasons so many cases of kidney decline go undetected, and how lifestyle choices—from protein intake to environmental toxins—can be both the problem and the path to healing. We get personal about the subtle symptoms, practical lab markers, and actionable steps you can take right now to protect your kidney health for the long term.   FREE GIFT: I made a free gift to thank you for listening: a quick list of my Top 5 Peptides. Grab yours here natniddam.com/top5. Episode Timestamps: Robin Rose's kidney journey ... 00:02:00 Kidney disease often missed ... 00:04:00 Early detection & eGFR ... 00:10:00 High protein diet caution ... 00:16:00 Kidney-friendly diet basics ... 00:25:00 Gut toxins & kidney health ... 00:27:00 Potassium, phosphorus labs ... 00:37:00 Mindset in recovery ... 00:39:00 Top kidney supplements ... 00:43:00 Peptides & bioregulators intro ... 00:47:00 Bioregulator dosing & cycling ... 00:52:00 Clotho & aging ... 00:57:00 Book & hopeful takeaway ... 01:04:00   Our Amazing Sponsors: Qualia Senolytic - A cutting-edge formula designed to help your body eliminate senescent cells, also known as “zombie cells.” Go to qualialife.com/NATHALIE  and use promo code NATHALIE to get 15% off—and try it risk-free with their 100-day money-back guarantee.   NEW Timeline Gummies: Urolithin A supports muscle strength and cellular energy. It's about improving how your body functions at the source. Mitopure is the only clinically proven Urolithin A, giving you 6 times more than you'd get from a glass of pomegranate juice. Visit Timeline.com/nat20 and use code nat20 for 20% off your purchase.   Ultimate GI Repair by LVLUP Health - Whether you're struggling with digestive discomfort or want to strengthen your gut health, Ultimate GI Repair provides the comprehensive support your body needs to restore balance. The ingredients are unmatched! Visit https://lvluphealth.com/ and use code NAT at checkout for 20 % off.   Nat's Links:  YouTube Channel Join My Membership Community Sign up for My Newsletter  Instagram  Facebook Group

The 2025 World Conference on Lung Cancer just concluded, and there are several notable updates concerning treatment of EGFR-mutated NSCLC. 1. The COMPEL study tries to find the value of continuing osimertinib (with the addition of chemotherapy) after progression on osimertinib. The results are, well, compelling! 2/3. We now have updates on the OS benefits of osimertinib + chemotherapy (FLAURA2) and amivantamab + lazertinib (MARIPOSA) compared to osimertinib monotherapy in initial treatment of metastatic disease. 4. NEOADAURA tries to determine if neoadjuvant osimertinib has value, but longer follow-up will be needed to assess this practice.

Are you up to date with therapy strategies for ALK translocation and EGFR mutation–positive non-small cell lung cancer? Credit available for this activity expires: 9/10/26 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1002896?ecd=bdc_podcast_libsyn_mscpedu

In this special WCLC 2025 episode of Lung Cancer Considered, hosts Dr. Narjust Florez and Dr. Stephen Liu discuss highlights from the conference. Dr. Susan Scott discusses EGFR mutant NSCLC and results from PALOMA-2 and subcutaneous amivantamab. Dr. Wenfeng Fang discusses Iza-Bren (BL-D01D1), a first-in-class EGFR x HER-3 biospecific ADC linked to a novel topoisomerase I inhibitor payload, with promising preliminary activity in EGFR positive previously treated NSCLC. Dr. Biagio Ricciuti shares his insights from WCLC 2025, including the FLAURA-2 OS readout, the HARMONi trial in EGFR positive NSCLC, and his research in the use of immunotherapy in early-stage lung cancer.

JCO fellow Dr. Ece Cali speaks with JCO Associate Editor Dr. Thomas E. Stinchcombe to discuss the JCO article "Phase 2 Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small-Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B)", that was simultaneously released at the IASLC 2025 World Conference on Lung Cancer. TRANSCRIPT Dr. Ece Cali: Hello, and welcome to our series where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's most important oncology meetings. I am your host, Dr. Ece Cali, JCO editorial fellow, and I am joined by Dr. Tom Stinchcombe, JCO associate editor, to discuss the Journal of Clinical Oncology article and 2025 World Conference on Lung Cancer abstract presentation, “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non–Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.” The WU-KONG1B trial is a multinational, phase II study that investigated the efficacy and safety of different doses of sunvozertinib in patients with metastatic non-small cell lung cancer and EGFR exon 20 insertion mutations after progression on platinum based chemotherapy. Tom, before we dive into the results, could you walk us through the rationale for this study, and how does it fit into the current treatment options for patients with EGFR exon 20 insertion? Dr. Tom Stinchcombe: Thank you, Dr. Cali. I think the clinical context is always important. We have known that EGFR exon 20 insertions exist and that they are resistant to our currently available EGFR tyrosine kinase inhibitors, and I think there have been attempts in the past to develop a tyrosine kinase inhibitor, but there is a very narrow therapeutic window between the dose you need to inhibit the EGFR mutation in the cancer and the EGFR receptor on normal tissues, most notably the mucosa, the gut, and the skin. And so, our previous attempts have failed largely because the dose required was not tolerable for patients and they could not really stay on the drug for a long time or they were not very active. And so, I think there was a real desire to develop an EGFR tyrosine kinase inhibitor, and then, historically, the standard had been a platinum based doublet as the standard of care. And more recently, platinum based doublet with amivantamab has proven to be superior to platinum based chemotherapy alone. I think the context is also important that amivantamab is not necessarily available in all the countries, and so, there are patients who do not have access to amivantamab. Going to the rationale, I think that this drug had shown preliminary promise of having activity but without that being encumbered by those EGFR wild type toxicities, and, therefore, it was really explored in this larger study. Dr. Ece Cali: And what are some key findings from this trial? Dr. Tom Stinchcombe: So, I think that we should look at the study design. It is a little quirky, for lack of a better term, in that there is a randomization to 200 versus 300 mg, and then, there was a nonrandomized cohort of 300 mg. So, when you look at the study, if you are a purist, you will just look at the randomized patients. If you are sort of an aggregator, you look at all patients. So, it shows reporting on three cohorts, but I think the key findings are that the 200 mg and the 300 mg treatments had similar toxicities in terms of response rate, duration of response, and progression free survival. And as you know going through the review, there was a lot of queries from the reviewers as to which would be the preferred dose, and to me, I think this really illustrates a dose finding component to a trial design because there is a lot of debate about what the minimal effective dose is or the optimal dose. And in this case, having the two dose cohorts did provide us some valuable efficacy and toxicity information. And then, when I look at the study, I want to make sure it reflects my patient population, and about a quarter of patients had brain metastases, and about 15% had previous amivantamab, and about 5% to 10% had another EGFR tyrosine kinase inhibitor. Dr. Ece Cali: And what is the objective response rate and the duration of response? These are pretty good numbers for this patient population. Dr. Tom Stinchcombe: In the 200 mg cohort, it was about 46%. The duration of response was around 11 months, and the PFS was around 8 months. The 300 mg cohort was 46%, duration of response 9.8, and the median PFS is 6.9 months, and I think that this is greater activity than we have seen with our previous attempts at EGFR tyrosine kinase inhibitors. Dr. Ece Cali: And based on these data, FDA granted accelerated approval for sunvozertinib very recently at 200 mg once daily dosing in this setting. So, that is a major step forward for our patients. Dr. Stinchcombe, how does this impact your clinical practice, and what side effects should oncologists be watching for if they prescribe this medication? Dr. Tom Stinchcombe: So, I think it was very interesting that they chose the 200 mg dose, which I think was more tolerable, and when we kind of look at this, there still was a rate of diarrhea, all grade, rash, paronychia, which are the EGFR related toxicities. There can be some decreased appetite, stomatitis, and then, it can lead to some lab abnormalities, like increased CPK and creatinine that physicians have to be aware of. You know, how it will affect my practice is that all these patients had received a platinum based chemotherapy as the first line therapy. I think that this would become my preferred second line therapy for patients outside the context of a trial because of the activity and the tolerability. Dr. Ece Cali: And lastly, several other tyrosine kinase inhibitors are being evaluated for EGFR exon 20 insertion, including in the frontline setting. So, what are some of the outstanding questions in this space, and what data should our listeners keep an eye on moving forward? Dr. Tom Stinchcombe: I think you are right that now, there is going to be another EGFR tyrosine kinase that may become available in the next year, and there is another drug, furmonertinib, that is being investigated. I think, for the clinical question, is, well, can we move these into the first line setting? And actually, the development path has two ways of doing this. There is EGFR tyrosine kinase compared to platinum based chemotherapy, and then, platinum based chemotherapy with an EGFR tyrosine kinase versus platinum based chemotherapy, and both have their merits and strengths. And so, I think it is going to be very interesting as we see if those first line trials, one, can they be demonstrated to be superior to platinum based chemotherapy, and then by what magnitude and what the side effects are. But I think we are hoping that in the next couple of years, we will have an additional first line option for our patients. Dr. Ece Cali: Yeah, it is always great to have more options for our patients. Thank you, Dr. Stinchcombe, for speaking about the JCO article, “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.” Join us again for the latest JCO simultaneous publications. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of World Lung Conference. 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.  

Neuropathic pain affects nearly 10% of the global population, yet effective treatments remain elusive. In this episode of Spark Time, we sit down with oncologists-turned-biotech-founders Christian Kersten and Marte Cameron of Akigai to hear the remarkable story of how a serendipitous clinical observation led to a new approach for treating chronic pain.From the first wheelchair-bound patient who walked again after EGFR inhibitor therapy, to the 100+ patients who have since experienced life-changing relief, Christian and Marte share the science and the vision behind Akigai's mission: to bring effective, non-opioid solutions to millions living with neuropathic pain. This is a story of discovery, persistence, and hope for one of medicine's most stubborn challenges.

Send us a textWhat if the AI tools we trust for cancer diagnosis are not always correct? This episode of DigiPath Digest takes on the uncomfortable but critical question: can AI “lie” to us—and how do we verify its performance before adopting it in clinical practice?Highlights:[00:02:00] Foundation models in action: Deployment of a fine-tuned pathology foundation model for EGFR biomarker detection in lung cancer—reducing the need for rapid molecular tests by 43%.[00:08:41] Bone marrow AI misclassifications: Why automated digital morphology still struggles with consistency across leukemia and lymphoma cases.[00:14:45] Lossy DICOM conversion: How file format changes can subtly—but significantly—affect AI model performance.[00:21:45] Federated tumor segmentation challenge: Coordinating 32 international institutions to benchmark healthcare AI fairly across diverse datasets.[00:27:47] AI in gynecologic cytology: Reviewing AI-driven Pap smear screening—promise, limitations, and why rigorous validation remains essential.[00:32:27] Takeaway: Trust but verify—AI tools must be validated before they can support or replace clinical decisions.Resources from this EpisodeNature Medicine – Fine-tuned pathology foundation model for lung cancer EGFR biomarker detection.Scientific Reports (Germany) – Study on how DICOM conversion impacts AI performance in digital pathology.Federated Tumor Segmentation Challenge – Benchmarking AI across 32 global institutions.Acta Cytologica – Review on AI in gynecologic cytology and Pap smear screening.Support the showBecome a Digital Pathology Trailblazer get the "Digital Pathology 101" FREE E-book and join us!

Are you aware of the latest developments for treating EGFR mutation–positive advanced/metastatic NSCLC? Credit available for this activity expires: 8/29/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1002869?ecd=bdc_podcast_libsyn_mscpedu

Jonathan Barratt, PhD, FRCP - The Nephrology Journal Club: B-Cell Modulators and eGFR Endpoints in IgA Nephropathy

Jonathan Barratt, PhD, FRCP - The Nephrology Journal Club: B-Cell Modulators and eGFR Endpoints in IgA Nephropathy

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. While the development of targeted therapies has improved outcomes for many patients with EGFR-mutated NSCLC, those with rare EGFR variants often face limited treatment options, especially when the disease involves the central nervous system (CNS). A recent research paper, titled “Durable complete response in leptomeningeal disease of EGFR mutated non-small cell lung cancer to amivantamab, an EGFR-MET receptor bispecific antibody, after progressing on osimertinib” published in Volume 16 of Oncotarget, describes a patient with NSCLC harboring two uncommon EGFR mutations—G719A and A289V—who experienced a prolonged and clinically significant response to amivantamab monotherapy, after prior treatments had failed. Full blog - https://www.oncotarget.org/2025/08/26/amivantamab-monotherapy-in-rare-egfr-mutated-advanced-nsclc/ Paper DOI - https://doi.org/10.18632/oncotarget.28730 Correspondence to - Young Kwang Chae - young.chae@northwestern.edu Video short - https://www.youtube.com/watch?v=UEiCz834a8c Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28730 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, amivantamab, monotherapy, rare EGFR mutation, NSCLC, leptomeningeal disease About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

In this episode of the Oncology Brothers podcast, Drs. Rohit & Rahul Gosain welcome Dr. Jacob Sands, a thoracic medical oncologist from the Dana-Farber Cancer Institute, to discuss the recent FDA approval of Dato-DXD (datopotamab deruxtecan) for previously treated EGFR-mutated non-small cell lung cancer (NSCLC). Key Topics: •⁠  ⁠Overview of Dato-DXd and its FDA approval •⁠  ⁠Mechanism of action and study design of the TROPION Lung trials •⁠  ⁠Efficacy and safety profile of Dato-DXd •⁠  ⁠Management of side effects and clinical pearls •⁠  ⁠Treatment sequencing for EGFR-mutated NSCLC Join us as we dive into the details of the TROPION Lung trials that led to this significant approval, the mechanism of action of Dato-DXd, and the implications for patients with various EGFR mutations.  Dr. Sands shared insights on the study design, efficacy, and tolerability of this new antibody-drug conjugate, as well as important clinical pearls for managing side effects such as stomatitis, dry eyes, and interstitial lung disease (ILD). We also explored the current treatment landscape for EGFR-mutated NSCLC, including the sequencing of therapies and the potential role of Dato-DXd in clinical practice. Tune in for an informative discussion that highlights the exciting advancements in oncology and the hope they bring to patients. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and check out our other episodes for more insights into the world of oncology!

BUFFALO, NY – August 15, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 13, 2025, titled “Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay.” In this study, first authors Valeriy Domenyuk and Kasey Benson, along with corresponding author David Spetzler from Caris Life Sciences in Irving, Texas, introduce MI Cancer Seek, an FDA-approved test designed to deliver comprehensive tumor profiling. MI Cancer Seek demonstrated strong concordance with other FDA-approved companion diagnostics and serves as a powerful tool to guide treatment decisions in both adult and pediatric cancer patients. Cancer remains one of the most complex and diverse diseases to treat. With many targeted therapies currently FDA-approved, selecting the right one for a specific patient requires detailed genetic insights. MI Cancer Seek addresses this need by analyzing both DNA and RNA from a single tumor sample. The tool identifies key biomarkers linked to FDA-approved treatments for several major cancers, including breast, lung, colon, melanoma, and endometrial cancers. One of the most significant strengths of MI Cancer Seek is its ability to deliver accurate and reliable results from minimal tissue input (50 ng). Even when analyzing formalin-fixed paraffin-embedded samples, which are widely used but often degraded, the test maintained high levels of accuracy. It successfully detected important genetic alterations such as PIK3CA, EGFR, BRAF, and KRAS/NRAS mutations and measured tumor mutational burden (TMB) and microsatellite instability (MSI), both of which are key indicators for immunotherapy response. In clinical comparisons, the test achieved over 97% agreement with other FDA-approved diagnostic tools, confirming its reliability in detecting critical biomarkers. Notably, it showed near-perfect accuracy in identifying MSI status in colorectal and endometrial cancers. The researchers also demonstrated that the test maintains precision across different lab conditions and varying DNA input levels, confirming its robustness for routine clinical use. Beyond its role as a companion diagnostic, MI Cancer Seek incorporates additional features developed under its predecessor, MI Tumor Seek Hybrid. These include detection of homologous recombination deficiency, structural variants, and cancer-related viruses. It also includes advanced tools such as the Genomic Probability Score for identifying the tissue of origin in cancers of unknown primary, as well as a gene signature to guide first-line chemotherapy in colorectal cancer. “One limitation to be considered is the low PPA for ERBB2 CNA detection.” By offering deeper genetic insights from a single, small sample, MI Cancer Seek has the potential to streamline diagnostics, reduce testing costs, and connect patients to effective therapies more quickly. As precision medicine continues to expand, this assay stands out as a comprehensive and efficient solution for meeting the evolving needs of modern oncology. DOI - https://doi.org/10.18632/oncotarget.28761 Correspondence to - David Spetzler - dspetzler@carisls.com Video short - https://www.youtube.com/watch?v=D4hd2FxCYY8 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

LCC in Cantonese: Novel Treatment for Advanced EGFR Mutant Lung Cancer by IASLC

Thank you for listening to The Peptide Podcast. If you enjoyed the show and want to support what we do, head over to our Partners Page. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going.  Today, we're diving into one of the most talked-about topics in health and weight loss right now: GLP-1 medications like semaglutide and the newer dual GIP/GLP-1s like tirzepatide. You've probably seen the headlines, scrolled past a few TikToks, or heard a friend mention it — but with all that noise comes a lot of confusion, half-truths, and flat-out myths. Today we're breaking it all down. What's real? What's hype? And what do you actually need to know if you're using these medications — or thinking about it? Let's separate science from scare tactics and get to the truth, one myth at a time. Myth #1: GLP-1s Cause Dangerous Muscle Loss The claim:  “GLP-1s cause massive muscle loss.” Truth: This is an overstatement. Some loss of lean mass is normal with any kind of weight loss — whether it's through diet, medication, or surgery. What studies show is that with medications like semaglutide (Wegovy) and tirzepatide (Zepbound), about 20–25% of the total weight lost comes from lean mass, and the rest is fat — which is exactly what we're targeting in obesity treatment. That 20–25% figure isn't unique to these meds; it's actually pretty typical in weight loss without focused resistance training or optimized protein intake. You may also hear “You'll lose all your muscle and become frail on GLP-1s.” Truth: You won't “lose all your muscle.” In fact, muscle loss is preventable by maintaining adequate protein intake, resistance training, and managing weight loss pace. Furthermore, many patients gain strength and mobility as excess weight comes off. And lastly, my favorite myth is “You can't preserve muscle on GLP-1s.” Truth: That's completely false — muscle loss isn't inevitable on GLP-1s if you take the right approach. You can absolutely preserve muscle by making a few intentional choices: aim for enough protein each day (a good goal is around 0.8 grams per pound of body weight), include some strength or resistance training a couple times a week, and avoid losing weight too quickly. These simple steps go a long way in protecting your lean mass while still getting all the benefits of weight loss. One study on semaglutide showed that people lost an average of about 15% of their body weight, and only around 3–4% of that was lean mass. So if someone drops 30 pounds, maybe 6 to 8 of those pounds might be lean mass—not ideal, but definitely not disastrous either, and very manageable with the right lifestyle habits.  The truth is, while some lean mass loss is expected with any type of weight loss, research shows that most of the weight lost on GLP-1s is actually fat, not muscle. For example, in the STEP 1 trial, about 80% of the weight lost on semaglutide came from fat, and only about 20% from lean tissue (as we mentioned earlier).  The SURMOUNT-1 trial with tirzepatide showed similar results—significant fat loss with relatively preserved muscle, especially when paired with resistance training. And that's important, because preserving muscle during weight loss helps protect metabolism, strength, and overall health. With good nutrition and movement, GLP-1s can lead to healthier body composition—not just a lower number on the scale. Okay, moving along to the next myth … Myth #2: GLP-1s Can Cause Blindness The truth: This myth stems from concerns about diabetic retinopathy worsening, which is tied to how quickly blood sugar drops, not to the drug itself. In the SUSTAIN-6 trial (Marso et al., NEJM, 2016), a small subset of patients with pre-existing advanced diabetic retinopathy saw transient worsening—but only in those with rapid improvements in A1c. No increased rates of blindness or new-onset retinopathy have been found in non-diabetic patients using GLP-1s for weight loss. The bottom line is that those without advanced diabetic eye disease, there's no increased risk of blindness. Patients with diabetic retinopathy should be monitored closely—but this is about glycemic management, not a direct effect of the medication. Myth #3: GLP-1s Cause Kidney or Liver Damage The truth: This is false. In fact, GLP-1 agonists may protect kidney and liver function—especially in patients with diabetes or fatty liver disease. The most recent notable study showing kidney‑protective effects of a GLP‑1 receptor agonist is the FLOW trial, which evaluated semaglutide in people with type 2 diabetes and chronic kidney disease (CKD). This double‑blind, randomized, placebo‑controlled trial included 3,533 participants followed for a median of 3.4 years and found that semaglutide reduced the risk of major kidney‑related events—including kidney failure, substantial eGFR decline, and death from renal or cardiovascular causes—by 24% compared to placebo. A 2025 meta-analysis of multiple randomized controlled trials (11 studies, 85,373 participants) concluded that GLP‑1 receptor agonists reduced the risk of composite kidney failure outcomes by 18%, kidney failure by 16%, and all‑cause death by 12%. And let's not forget the SMART trial, involving obese patients with kidney disease but without diabetes, found that semaglutide protected kidney function in this non‑diabetic, CKD‑affected population.  When it comes to the liver, there's actually growing evidence they're actually helping reverse non-alcoholic fatty liver disease (NAFLD). The STEP 1 MRI substudy and SURPASS-3 MRI substudy have shown people on these medications can reduce liver fat by 30 to even 50% and in some cases, completely resolve liver inflammation — that more serious form called NASH, where fat is combined with inflammation and early scarring. The LEAN trial found that nearly 60% of people taking semaglutide had resolution of NASH, without worsening their liver scarring. That's huge. And even better, we're seeing these effects even in people who don't have diabetes. Just losing weight helps fatty liver, but these meds seem to do more than that — they actually target inflammation and fat storage in the liver itself.. The bottom line is GLP-1s are not nephrotoxic or hepatotoxic. In fact, they may be organ-protective—especially for people with underlying metabolic issues. Myth #4: These Drugs Lead to Bone Loss The claim: “You'll get osteoporosis from losing too much weight!” The truth: While extreme weight loss can affect bone density, GLP-1s themselves do not cause bone loss, and may even have neutral or protective effects on bone. A 2022 study in Bone found no significant change in BMD (bone mineral density) in adults treated with semaglutide for obesity. While the SUSTAIN and PIONEER programs found no increased risk of fractures in semaglutide-treated patients versus placebo. Truly, concerns about bone loss are more relevant in extreme calorie restriction or eating disorders—not evidence-based GLP-1 treatment with appropriate nutrition. Myth #5: Everyone Gets Gastroparesis The claim: “These medications paralyze your stomach” The truth: GLP-1s slow gastric emptying, which is part of how they work—making you feel full longer. But this is dose-dependent and typically reversible. A 2023 FDA safety review found that true gastroparesis is extremely rare and resolves when the drug is stopped. Reality check: Nausea, early satiety, and mild bloating are common but manageable side effects. True, lasting gastroparesis is not typical, especially when doses are titrated gradually. Myth #6: GLP-1s Make Your Hair Fall Out The claim: “You'll lose a ton of hair—just like with crash diets” The truth: Hair shedding is not directly caused by GLP-1 medications. Instead, it's often a temporary, non-scarring condition called telogen effluvium, which can happen with any rapid weight loss, regardless of the method. A 2023 analysis from the American Academy of Dermatology emphasized that telogen effluvium is common with surgical or medical weight loss, especially if patients lose more than 10% of their body weight within a few months. In clinical trials like STEP and SURMOUNT, hair loss was not listed as a common side effect, but patient-reported data show it occurs occasionally—likely tied to nutritional stress, not the drug itself. So why does hair loss happen? We've talked about this before, but I don't want to leave this important information out.  Hair follicles are sensitive to internal stress. Rapid changes in caloric intake, nutrient levels (like iron, zinc, and biotin), or hormone balance can push hairs into the shedding phase. This is a delayed effect, often showing up 2–3 months after weight loss begins, and it typically resolves within 6–12 months. What helps is slower, sustained weight loss, prioritizing protein intake, supplementing iron, zinc, and biotin if deficient, and avoiding very low-calorie diets and over-restriction. Myth #6: GLP-1s Cause Dehydration It's a common myth that GLP-1 medications cause dehydration — but that's not exactly true. The medication itself doesn't directly dehydrate you. What can happen is that some people experience nausea, vomiting, or a reduced appetite early on, which can lead to drinking less water without realizing it. That's where the dehydration risk comes in. A good general rule for staying hydrated is to aim for half your body weight in ounces of water per day. So, for example, if you weigh 160 pounds, try to drink around 80 ounces daily — more if you're active or live in a hot climate. Electrolytes can also be really helpful, especially if you're feeling tired, dizzy, or crampy. I like LMNT packets — they're a clean option with no sugar and a good balance of sodium, magnesium, and potassium. The sodium in LMNT packets helps keep you hydrated by pulling water into your cells and helping your body retain the fluids it needs to function properly. Just one a day can make a big difference in how you feel. Myth #7: You Have to Stay on GLP-1s Forever or You'll Gain All the Weight Back The claim: “As soon as you stop taking it, all the weight comes back” The truth: Yes—some weight regain is likely after stopping GLP-1 medications. But that doesn't mean they're ineffective or that you're doomed to rebound completely. The same pattern happens after any type of weight loss intervention, whether it's a diet, surgery, or medication. The STEP 4 trial (Wilding et al., 2022) showed that participants who stopped semaglutide after 20 weeks regained an average of 6% of their weight loss over the next year. But it's important to note that they still weighed less than at baseline—and many continued to experience improvements in blood pressure, cholesterol, and insulin sensitivity. Similarly, in SURMOUNT-4, patients who stopped tirzepatide also regained weight, but less than they lost. So why does this weight gain happen? I feel like the answer to this is obvious, but I've found that it's not.  GLP-1s change your appetite and hunger cues. Once the medication is stopped, your body's baseline hunger signals return—and often with increased intensity, due to metabolic adaptation. But this isn't unique to GLP-1s. The same thing happens after crash diets, keto, intermittent fasting, or bariatric surgery if long-term changes aren't made. The real issue isn't the drug—it's the lack of a plan after the drug. To help make results sustainable, we need to use the medication as a tool, not a crutch. We should use it to help us lose weight and understand our hunger cues, while transitioning to a whole foods, protein based diet coupled with resistance training to help preserve and build muscle.  Just remember, if you're coming off a GLP-1 and want to keep the momentum going, the key is to approach it thoughtfully. Tapering slowly under medical supervision can help your body adjust and reduce the chances of weight regain. At the same time, this is a great moment to double down on the habits that helped you feel your best while on the medication. Think ongoing support—like working with a health coach, joining a support group, or even doing behavioral therapy—to help reinforce those long-term lifestyle changes. It's not just about what you stop; it's about what you keep doing that matters most. You don't necessarily have to stay on GLP-1s forever—but if you stop without a plan, some weight regain is very likely. Think of them like glasses: they help you see clearly while you build the habits to eventually navigate without them. For some, that may mean staying on a lower maintenance dose long-term—just like with blood pressure or cholesterol meds. What are my final thoughts? I want to be clear—GLP-1s aren't magic. But they are powerful tools when paired with education, support, and smart lifestyle changes.  Myths like ‘you'll go blind,' ‘you'll lose all your hair,' or ‘you'll be stuck on these meds forever' aren't just misleading and downright false—they discourage people from getting real help.  So if you're thinking about these medications, get informed, ask the hard questions, and make your decision based on science—not fear. Thank you for listening to The Peptide Podcast. If you enjoyed the show and want to support what we do, head over to our Partners Page. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going.  Until next time, be well, and as always, have a happy, healthy week.

Imagine you've been on the kidney transplant waitlist for years, hoping for a second chance at life. Then, one day, you find out that your estimated wait time was longer than it should have been—not because of your health, but because your kidney function was calculated using a race coefficient. That was the reality Black kidney patients faced. Now, that's changing. Dr. Vinay Nair, the Medical Director at North Shore University Hospital and Northwell Health, Morgan Reid, NKF's former Senior Transplant Policy and Strategy Director, and two kidney warriors Michele Bibby and Brittany Dickerson are here to break down the impact of removing race from eGFR and what that means for transplant patients   In today's episode we spoke to:  Dr. Vinay Nair, is an Associate Professor of Medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/ Northwell and the medical director of kidney transplantation for Northwell Health. Dr. Nair's clinical and research interests include novel immunosuppressive protocols, kidney paired exchange and infectious and malignant complications after transplantation. He serves as part of CERCA (coalition to end racism in clinical algorithms), the editorial board and reviewer of several nephrology and transplant journals, and has served in the UNOS kidney transplantation committee. Dr. Nair has published on various transplant related topics and co-authored book chapters on immunosuppression and post-transplant malignancy. He is an advocate for equality in medicine and has spoken at several community outreach events on the importance of chronic kidney disease recognition and kidney transplantation. Michele Bibby is President of MAB Consulting Services. Michele provides mental health education, advocacy, and policy analysis to public and private entities. Michele designs and delivers mental health workshops and training.  Michele delivers public speeches and presentations on mental health topics. Michele Bibby previously enjoyed a successful career in Human Resources Management in the Private and Public Sector.  Michele has a Professional in Human Resources (PHR) Certification. Michele is a Certified Peer Specialist and a Certified Mediator. Michele serves as Board Chair for Via Hope a Texas Mental Health Nonprofit.  Michele also serves on the National Kidney Foundation “Kidney Advocacy Committee” and the “Health Equity Sub Committee”. Michele holds a B.A. in Government from The University of Texas at Austin (1984).  Morgan Reid is the Regional Patient Advocacy Manager for Ardelyx, Inc.  Previously, she worked at the National Kidney Foundation as the Senior Director of Healthcare Policy and Strategy. She is a tireless patient advocate and also a kidney recipient herself. Brittany Dickerson- I am a dedicated mother, motivational speaker, and compassionate life coach living with Polycystic Kidney Disease (PKD). I use my kidney failure battle to educate and help others regarding kidney disease and transplantation. My personal journey has fueled my passion for helping others navigate life's challenges with courage and grace. Through partnership with the National Kidney Foundation, I have had the opportunity to mentor others and to be a guest for the National Kidney Foundation Podcast channel. My dedication to kidney awareness has led me to pursue becoming a National Kidney Foundation Advocate. I use my voice to spread my powerful message of perseverance and hope. My goal is to continue making an impact on individuals facing adversity, offering guidance, support, and being a shining example of strength in the face of hardship.    Additional Resources: Removing Race-Based eGFR   Do you have comments, questions, or suggestions? Email us at NKFpodcast@kidney.org. Also, make sure to rate and review us wherever you listen to podcasts.  

LCC in Romanian: Management of Unresectable, EGFR-mutated Stage III Lung Cancer in Romania by IASLC

“Colorectal cancer treatment is not just about eliminating a disease. It's about preserving life quality and empowering patients through every phase. So I think nurses are really at the forefront that we can do that in the oncology nursing space. So from early detection to survivorship, the journey is deeply personal. Precision medicine, compassionate care, and informed decision-making are reshaping outcomes. Treatment's just not about protocols. It's about people,” ONS member Kris Mathey, DNP, APRN-CNP, AOCNP®, gastrointestinal medical oncology nurse practitioner at The James Cancer Hospital of The Ohio State University Wexner Medical Center in Columbus, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about colorectal cancer treatment.  Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 1.0 contact hour of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by August 1, 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 treatment of colorectal cancer. Episode Notes  Complete this evaluation for free NCPD. ONS Podcast™ episodes: Episode 370: Colorectal Cancer Screening, Early Detection, and Disparities Episode 153: Metastatic Colorectal Cancer Has More Treatment Options Than Ever Before ONS Voice articles: Colorectal Cancer Prevention, Screening, Treatment, and Survivorship Recommendations Genetic Disorder Reference Sheet: Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) How Liquid Biopsies Are Used in Cancer Treatment Selection Oncology Drug Reference Sheet: 5-Fluorouracil Oncology Drug Reference Sheet: Oxaliplatin What Is a Liquid Biopsy? Clinical Journal of Oncology Nursing article: Colorectal Cancer in Young Adults: Considerations for Oncology Nurses Oncology Nursing Forum article: Neurotoxic Side Effects Early in the Oxaliplatin Treatment Period in Patients With Colorectal Cancer ONS Colorectal Cancer Learning Library ONS Biomarker Database (filtered by colorectal cancer) ONS Peripheral Neuropathy Symptom Interventions American Cancer Society colorectal cancer resources CancerCare Colorectal Cancer Alliance Colorectal Cancer Resource and Action Network Fight Colorectal Cancer National Comprehensive Cancer Network 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 “Colorectal cancer has several different types, but there is one that dominates the landscape, and that is adenocarcinoma. So I think most of us have heard that. It's fairly common, and it accounts for about 95% of all colorectal cancers. It begins in the glandular cells lining the colon or rectum and often develops from polyps, in particular adenomatous polyps.” TS 1:41 “One of the biomarkers that we'll most commonly hear about is KRAS or NRAS mutations. This indicates tumor genetics, and these mutations suggest resistance to our EGFR inhibitors such as cetuximab. BRAF mutation or V600E is a more aggressive tumor subtype, and those may respond to our BRAF targeted therapy. … And then our MSI-high or MMR-deficient—microsatellite instability or mismatch repair deficiency—that really predicts an immunotherapy response and may indicate Lynch syndrome, which is a huge genetic component that takes a whole other level of counseling and genetic testing with our patients as well.” TS 6:02 “Polypectomy or a local excision—that removes our small tumors or polyps during that colonoscopy. And that's what's used for those stage 0 or early stage I cancers. A colectomy removes part or all of the colon. This may be open or laparoscopic. It can include a hemicolectomy, a segmental resection, or a total colectomy, so where you take out the entire part of the colon. A proctectomy removes part or all of the rectum. This may include a low anterior resection, also known as an LAR … or an abdominal perineal resection, which is an APR. … Colostomy or ileostomy—that diverts the stool to an external bag via stoma. Sometimes this is temporary or permanent depending on the type of surgery.” TS 14:11 “We'll have our patients say, ‘Hey, I want immunotherapy therapy. I see commercials on it that it works so well.' We have to make sure that these patients are good candidates for it, also that we're treating them adequately. We need to make sure that they have those biomarkers, so as I mentioned, the MSI-high or MMR tumors. Our MSS-stable tumors—they may benefit from newer combinations or clinical trials. Metastatic disease—immunotherapy may be used alone or with other treatments. And then in the neoadjuvant setting, some trials are really showing promising results using immunotherapy prior to surgery.” TS 25:38 “Antibody-drug conjugates are really an exciting frontier in all cancer treatments as well as colorectal cancer treatment. This is used mainly for patients with advanced or treatment-resistant disease, and these therapies combine the targeted power of monoclonal antibodies with the cell-killing ability of potent chemotherapy agents. They're still on the horizon for the most part in colorectal cancer. However, there is only one approved antibody-drug conjugate, or ADC, at this time, and that's trastuzumab deruxtecan, or Enhertu. That's approved for any solid tumor, such as colorectal cancer with HER2 IHC 3+. So again, looking back at that pathology in those markers, making sure that you have that HER2 mutation and that IHC.” TS 35:00 “There are a few myths going around about colorectal cancer treatment that can lead to confusion or even delayed care. One myth is only older men get colorectal cancer. As you heard me talk in my previous podcast on screening, unfortunately, this isn't necessarily true. Colorectal cancer affects both men and women and our cases in the younger population are rising. So our screening guidelines have changed to age 45 because we are seeing it in the younger population.” TS 45:54

What does effective kidney care look like in the primary care setting—and who's really involved beyond your GP? In this first of a special two-part series, host Dee Moore is joined by Dr. Kristin Veighey to explore the crucial yet often misunderstood role of primary care in managing chronic kidney disease (CKD).   This episode takes you beyond the GP, highlighting the power of the multidisciplinary team—including specialist nurses, pharmacists, health coaches, social prescribers, and mental health professionals—and how each plays a unique role in supporting kidney health.   Together, they discuss: • The definition and purpose of primary care vs. secondary care • Why CKD is often overlooked or mismanaged in primary care settings • The impact of legacy thinking, outdated guidelines, and unclear care pathways • How to navigate the system, understand who does what, and advocate for yourself • The importance of tracking your eGFR, blood pressure, and asking the right questions during health checks   This empowering episode is designed to help you take control of your kidney health journey by understanding your rights, responsibilities, and the full range of support available to you.  

In today's episode, we spoke with Joshua K. Sabari, MD, about the use of telisotuzumab vedotin-tllv (Emrelis) in patients with c-MET–overexpressing, nonsquamous, EGFR wild-type advanced non–small cell lung cancer (NSCLC). Dr Sabari is an assistant professor in the Department of Medicine at the New York University Grossman School of Medicine; as well as the director of High Reliability Organization Initiatives at the Perlmutter Cancer Center in New York.  In our exclusive interview, Dr Sabari highlighted key data from the phase 2 LUMINOSITY study (NCT03539536) investigating telisotuzumab vedotin in this patient population, the significance of targeting c-Met overexpression, and how findings from the ongoing phase 2 TeliMET NSCLC-04 trial (NCT06568939) of telisotuzumab vedotin in patients with c-Met–overexpressing, locally advanced or metastatic nonsquamous NSCLC may further influence the NSCLC treatment paradigm. 

In this episode, we discuss the evidence, safety, and place in therapy of Journavx® (suzetrigine), a newly approved analgesic with a unique non-opioid mechanism of action and additional considerations for its use. Key Concepts Suzetrigine is a first in its class NaV1.8 sodium channel blocker approved for short-term (14 days or less) pain relief in adults with moderate-to-severe pain. Unlike opioids, suzetrigine is non-sedating and non-dependence forming. Suzetrigine is taken as a whole pill without cutting, crushing, or chewing following a particular dosing schedule where the first dose is taken on an empty-stomach.  The most common side effects of suzetrigine include pruritus, muscle spasms, increased CPK, rash, and transient (reversible) eGFR decrease. Suzetrigine goes through CYP3A metabolism and therefore has significant interactions with CYP3A inducers and inhibitors. Use with strong inhibitors and moderate to strong inducers is not recommended. Dose reduction of suzetrigine is required if used with moderate inhibitors of CYP3A.  Although not formally adopted in a guideline recommendation, suzetrigine's current place in therapy can be moderate-to-severe acute pain relief in adult patients after NSAIDs/APAP options are exhausted, but before or in place of opioid therapy.  References Bertoch T, D'Aunno D, McCoun J, et al. Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials. Anesthesiology. 2025;142(6):1085-1099. doi:10.1097/ALN.0000000000005460

FDA Approval: Datopotamab Deruxtecan for EGFR NSCLC by IASLC

Dr. Joshua Reuss joints that podcast to discuss the latest changes to the living guideline on stage IV NSCLC with driver alterations. He discusses the new evidence for NSCLC with EGFR mutations and NRG1 fusions and how this impacts the latest recommendations from the panel. He shares ongoing research that the panel will review in the future for further updates to this living guideline, and puts the updated recommendations into context for clinicians treating patients with stage IV NSCLC. Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2025.1” at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-01061 Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Joshua Reuss from Georgetown University, co-chair on "Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2025.1." It's great to have you here today, Dr. Reuss. Dr. Joshua Reuss: Thank you. Happy to be here. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Reuss, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So to dive into what we're here today to talk about, Dr. Reuss, this living clinical practice guideline for systemic therapy for patients with stage IV non–small cell lung cancer with driver alterations is updated on an ongoing basis. So what prompted this latest update to the recommendations? Dr. Joshua Reuss: Yes, thank you. It's very important that we have living guidelines that are continuously updated. We obviously don't live in a static environment where things are non-changing, and we really need to apply the most up-to-date and current evidence to treat our patients with the most effective strategies, the most groundbreaking strategies. And so to have guidelines that can be disseminated, particularly these ASCO guidelines, to treating providers is incredibly important. So, with any of these updates, we review ongoing studies, published work, for the quality of evidence to see if it's something that warrants making adjustments to our guidelines or at least incorporating the information so that providers can review it and incorporate this into their own personal decision-making. So in this particular update, we reviewed evidence particularly pertaining to EGFR-mutated non–small cell lung cancer and non–small cell lung cancer harboring an NRG1 fusion. Brittany Harvey: Yes, certainly there's a lot of new evidence in the advanced non–small cell lung cancer field, and so we appreciate the panel's continuous review of this evidence. So then you just mentioned two separate areas where the panel reviewed new evidence. So starting with that first one, what updated evidence did the panel review on first-line treatment options for patients with EGFR alterations, and how did this impact the recommendations? Dr. Joshua Reuss: Yes, so advanced EGFR-mutated non–small cell lung cancer, at least with classical activating alterations - that is our exon 19 deletions and our exon 21 L858R mutations - is something that's really evolved rapidly in the last few years. You know, for many years, we basically, for the frontline treatment setting, were saying, "Okay, we have a targeted therapy, osimertinib. We're going to give that, and we're going to see what effect we can get out of that," with, you know, a median time of duration of treatment response averaging around 18 months, knowing that there are some that that's a lot longer and some that are a lot shorter. But recently, we've seen a lot of data emerging on combination strategies. The guideline has already been updated to incorporate two of these combinations: osimertinib with chemotherapy based off of the FLAURA2 trial, and then the combination of amivantamab with lazertinib based off of the MARIPOSA trial. And that was data on progression-free survival that was published and led to those particular recommendations. Now, more recently, we've seen data come out in smaller, randomized studies for other combinations. And more recently, we reviewed the RAMOSE study. So this was a phase II, open-label, randomized trial for patients with tyrosine kinase inhibitor–naive and really, treatment-naive advanced EGFR-mutated non–small cell lung cancer harboring one of these two classical EGFR alterations, randomized to either osimertinib alone or osimertinib with the combination of ramucirumab, which is an anti-VEGF agent. There's been a lot of data, preclinical and clinical, for the role of VEGF blockade, particularly in EGFR-mutated non–small cell lung cancer, so exploring the combination of this for synergy in the frontline setting really made a lot of sense. So again, this was a phase II trial that randomized patients prospectively to one of these two regimens. The population here is really what we typically see with EGFR-mutated non–small cell lung cancer, predominantly a younger population - median age on this study was 65 - predominantly female - 71% female - and predominantly nonsmokers. Now, what this study showed was that at a median follow-up of 16.6 months, the progression-free survival favored the combination arm with a median progression-free survival of 24.8 months with the combination of osimertinib plus ramucirumab versus 15.6 months for osimertinib alone, for a hazard ratio of benefit of 0.55. The landmark one- and two-year endpoints for progression-free survival also favored the combination arm, and response rates were relatively comparable between groups, with overall adverse events being more frequent in the combination group, specifically high blood pressure, proteinuria, and epistaxis, which are our common adverse events related to VEGF-blocking agents. So, it's good to see data in this space. Now, of note, though, this was a phase II study, so not a phase III level of evidence. In addition, when looking at the population, this was a randomized, multicenter study, but it was a US-only population. There was also some imbalance in the number of visits between arms, so the combination arm was seen more frequently than the arm that got osimertinib alone. Now, the imaging assessments were no different, but obviously this could lead to potential confounding, at least in timing of awareness of potential side effects and and things being brought to the attention of investigators. So very promising data here, but because, you know, of this being a phase II study, this actually led to no changes in the guideline at this time. Brittany Harvey: Understood. Yes, as you mentioned prior, it's important to understand the full body of evidence and to review the trials even when it doesn't impact the recommendations. Dr. Joshua Reuss: And I will say that, you know, there is an ongoing phase III study looking at a very similar combination. It's the phase III ECOG-ACRIN trial of the combination of osimertinib plus bevacizumab versus osimertinib alone in this specific population. So, you know, I think we will see phase III–level data for a combination of VEGF with osimertinib, but again, promising phase II data that did not lead to a change in the recommendation at this time. Brittany Harvey: Absolutely. We'll look forward to that ongoing trial to learn more about combination in this patient population. So then moving to that second patient population that you mentioned earlier where the panel reviewed evidence, what is the updated evidence and recommendation for patients with NRG1 fusions? Dr. Joshua Reuss: Yeah, so this was an exciting update that we made more recently with this unique iteration of the living guidelines. So, NRG1 fusions, this is perhaps a newer kid on the block in terms of driver alterations that has been known to be identified in non–small cell lung cancer among other solid tumors. It is very rare, occurring in less than 1% of solid tumors, but something that we know is a unique oncogenic pathway that can lead to oncogenesis and cancer development, including in non–small cell lung cancer. So up until now, unfortunately, there have not been targeted therapies that target this unique alteration. It's somewhat different than other driver alterations where there's a top-level signaling change in a protein. This is more of a ligand alteration that then alters, that then enables activation of more classical pathways, but again, through upregulation of a unique ligand. So a slightly different pathway but something that we know should be able to be targeted to promote patient survival for those with NRG1 fusions. So the therapy here is a therapy called zenocutuzumab. It's an IgG1 bispecific antibody against HER2 and HER3. So it prevents the downstream dimerization and signaling that occurs as a result of this NRG1 fusion and upregulation of the NRG1 signal. This was, as you can imagine with a rare alteration, a large phase II registrational study that examined this in advanced solid tumors containing the NRG1 fusion. This is the NRG1 registrational trial. And this study enrolled patients with advanced solid tumors who had progressed on prior therapy. Patients were treated with zenocutuzumab 750 milligrams IV every two weeks. Among 158 response-evaluable solid tumor patients, the response rate was 30%, median duration of response of 11.1 months, and a median progression-free survival of 6.8 months. Now, in those with non–small cell lung cancer, that made up 93 response-evaluable patients, very similar outcomes there: a response rate of 29%, median duration of response of 12.7 months, and a median progression-free survival of 6.8 months. This therapy did appear to be well tolerated. The most common higher-grade emergent side effects - grade 3 or higher - were anemia occurring in 5% and elevated liver numbers occurring in 3%. So this is a subsequent-line study, so this led to the updated recommendation that clinicians may offer zenocutuzumab in the subsequent-line setting for patients with advanced non–small cell lung cancer who harbor NRG1 fusions. So I think this does speak toward the incredible importance of next-generation sequencing and molecular testing for patients, particularly to include testing that looks at the RNA. These large fusions can sometimes be very challenging to detect on DNA sequencing platforms alone, so it's important to, if you have a high level of suspicion for an alteration like this, perhaps some of the mucinous adenocarcinomas where it's been challenging to find a driver alteration, and it's someone who is a never-smoker, really would want to include molecular testing that assesses the RNA level and not just the DNA. Brittany Harvey: Absolutely. It's important to have all the biomarkers available so that clinicians are able to use that to inform their decision-making. So then, given these changes in the guideline, what should clinicians know as they implement this latest living guideline update? And how do these changes impact patients? Dr. Joshua Reuss: Yeah, I think talking in reverse order of what we just discussed here, there is a new guideline update for NRG1 fusions. So I think making sure that that's being evaluated, that clinicians are testing for that and really looking for that result that should be incorporated in in most next-generation large sequencing assays to get that result, but it's very important that that is not overlooked now that we do have a therapy that's available in the subsequent-line setting, though it is important to note that patients with NRG1 fusions, at least the limited data that there is suggests that the efficacy to standard chemoimmunotherapy regimens is overall poor. So physicians unfortunately might be facing this question for second-line therapy in patients with NRG1 fusions sooner rather than later. For the former, for EGFR-altered non–small cell lung cancer and how do we incorporate VEGF-containing regimens into these patients? Our guideline top-level update did not change based off of review of this new study, but it's important for clinicians to know what other combinations may exist. You know, there are phase III studies looking at this combination in the frontline setting. And of course, there is data on other bispecific molecules that incorporate VEGF in the subsequent-line setting, particularly a combination that includes the VEGF/PD-1 bispecific antibody ivonescimab that's being studied in the HARMONi-A trial for patients with EGFR-mutated advanced non–small cell lung cancer, for which we hope to get some more definitive data in the coming months. Brittany Harvey: Definitely. And then you've just mentioned a few ongoing trials where we're looking for evidence to inform future updates. But thinking beyond that, into the future, what is the panel examining for future updates to this living guideline? Dr. Joshua Reuss: It's a very exciting time to be in the world of treating advanced non–small cell lung cancer, particularly patients with driver alterations, because there is so much evolving data that's changing our practice in real time, again highlighting the importance of these living guideline updates. I'd say there's many things that we're excited to see. You know, a lot of the combination regimens in EGFR-mutated non–small cell lung cancer for which there are approvals and current recommendations in our guideline, particularly osimertinib plus chemotherapy and amivantamab plus lazertinib - those are the two approved combination strategies in the front line - we are now seeing the emergence of overall survival data for those combinations. So obviously that is something that's going to be very important for the committee to review and incorporate into guideline updates. There are several new therapies coming down the road for other driver populations. We recently saw an approval for taletrectinib for ROS1 fusion–positive non–small cell lung cancer, so it's going to be important that the committee reviews the data and the publications regarding that therapy. And then there are other novel therapies that we're looking to see updated data on. There are multiple antibody-drug conjugates, which take the potent power of a chemotherapy molecule and attempt to make that targeted with an antibody targeting to a unique feature on the cancer cell. And there are several antibody-drug conjugates that are in development at various levels of promise in this space, particularly in EGFR-mutated non–small cell lung cancer, and I anticipate seeing some emerging data for that coming up in the near future as well. So really, lots to be excited in the space and lots for our committee to review to give guidance on so that these patients can really receive the top-level care wherever they are being treated in the country and throughout the world. Brittany Harvey: Yes, we'll await this new data to continue to provide optimal options for patients with stage IV non–small cell lung cancer with driver alterations. So, Dr. Reuss, I want to thank you so much for your work to rapidly and continuously update and review the evidence for this guideline and thank you for your time today. Dr. Joshua Reuss: Thank you so much. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available on the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

FDA Approval: Sunvozertinib for EGFR Exon 20 by IASLC

In today's episode, supported by Thermo Fisher Scientific, we had the pleasure of speaking with Apar Kishor Ganti, MD; and Allison Cushman-Vokoun, MD, PhD, FCAP, about the FDA approval of the Oncomine DX Express Test for use as a companion diagnostic for sunvozertinib (Zegfrovy) in EGFR exon 20 insertion mutation–positive non–small cell lung cancer and for use in tumor profiling. Dr Ganti is a professor in the University of Nebraska Medical Center (UNMC) Division of Oncology & Hematology, the Dr. and Mrs. D. Leon UMNC Research Fund Chair in Internal Medicine, and the associate director for Clinical Research at the Fred & Pamela Buffett Cancer Center in Omaha. Dr Cushman is the Henry F. Krous Professor of Pathology, a professor in the UNMC Department of Pathology, Microbiology and Immunology, director of the Division of Diagnostic Molecular Pathology and Human Genetics, medical director of the Molecular Diagnostics and Personalized Medicine Laboratory at Nebraska Medicine, director of the Molecular Genetic Pathology Fellowship Program, and associate director of the UMNC MD-PhD Scholars Program.  In our exclusive interview, Drs Ganti and Cushman discussed the significance of the launch of the Oncomine DX Express Test, the benefits and limitations of rapid next-generation sequencing, and features that set Oncomine DX apart from other available tests. 

Welcome to HCPLive's 5 Stories in Under 5—your quick, must-know recap of the top 5 healthcare stories from the past week, all in under 5 minutes. Stay informed, stay ahead, and let's dive into the latest updates impacting clinicians and healthcare providers like you! Interested in a more traditional, text rundown? Check out the HCPFive! Top 5 Healthcare Headlines for June 30-July 6, 2025: Sebetralstat FDA-Approved as First Oral, On-Demand for Hereditary Angioedema The FDA approved sebetralstat (Ekterly) on July 7, 2025, as the first oral, on-demand treatment for hereditary angioedema attacks in patients aged 12 and older, backed by phase 3 KONFIDENT trial data. Rilparencel Improves eGFR Slope in Phase 2 CKD, Diabetes REGEN-007 Trial Rilparencel significantly slowed kidney function decline in CKD patients with diabetes in the REGEN-007 trial, showing dose-responsive eGFR slope improvements after two injections per kidney. J&J Submits sNDA to FDA for Lumateperone (CAPLYTA) to Prevent Schizophrenia Relapse J&J filed a supplemental NDA for lumateperone after phase 3 data showed a 63% reduction in schizophrenia relapse risk compared to placebo. FDA Publishes CRLs for Past Drug, Biological Product Applications The FDA publicly released over 200 Complete Response Letters from 2020–2024 to increase regulatory transparency and help accelerate future drug approvals. FDA Grants TSND-201 Breakthrough Therapy Designation for PTSD TSND-201 (methylone) received Breakthrough Therapy designation for PTSD on July 10, 2025, offering a potential rapid-acting alternative to SSRIs, which can take up to 12 weeks for full effect.

BUFFALO, NY – July 9, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 25, 2025, titled “Challenges and resistance mechanisms to EGFR targeted therapies in head and neck cancers and breast cancer: Insights into RTK dependent and independent mechanisms.” Researchers from the University of Cincinnati and Cincinnati Veterans Affairs Medical Center reviewed current research on why Epidermal Growth Factor Receptor (EGFR)-targeted therapies often fail in breast and head and neck cancers. The article by Shreya Shyamsunder, Zhixin Lu, Vinita Takiar, and Susan E. Waltz explores how cancer cells evade these treatments by activating alternative survival pathways. This review offers an in-depth look at the molecular barriers to EGFR inhibition and provides insights that could inform the development of more effective and durable treatments. EGFR is a critical protein that regulates cell growth and survival, and it is frequently overexpressed in breast and head and neck cancers. Although therapies targeting EGFR showed early promise, resistance has become a significant challenge. In breast cancer, resistance mechanisms include the movement of EGFR from the cell surface into the nucleus, where it promotes DNA repair, as well as ligand-dependent activation that helps tumor growth despite therapy. In head and neck cancers, resistance often arises from inflammatory signaling through the TLR4-MyD88 pathway and the loss of tumor suppressor genes like PTEN, which allow cancer cells to bypass EGFR inhibition. The review also describes how tumor cells in both cancers commonly activate other receptor tyrosine kinases (RTKs), such as MET, AXL, and RON, to continue growing even when EGFR is blocked. By analyzing these resistance mechanisms, the authors highlight combination therapies from current research that target EGFR and other key molecular pathways. Strategies such as dual inhibition of EGFR and MET or blocking inflammation-driven survival signals may enhance treatment outcomes. Several clinical trials are evaluating these approaches in patients. For example, in breast cancer, combinations of EGFR inhibitors with chemotherapy and immune checkpoint inhibitors are being tested to improve responses, particularly in triple-negative breast cancer. In head and neck cancers, trials are investigating EGFR-blocking antibodies like cetuximab combined with immunotherapies such as pembrolizumab and nivolumab. These efforts aim to overcome resistance and provide more effective treatment options for patients with EGFR-driven tumors. The review also emphasizes the necessity of identifying biomarkers to predict which patients are most likely to benefit from EGFR-based therapies. “A recent phase 1 study has shown that patients with recurrent or metastatic head and neck cancer who received BCA101, a bifunctional dual targeting drug that targets EGFR and TGF-β in combination with pembrolizumab, were able to achieve an overall response rate of 65%.” This work brings together current knowledge about EGFR resistance and illustrates the difficulties involved in treating breast and head and neck cancers. By mapping the many ways tumors overcome EGFR inhibition, the review highlights opportunities for more tailored and effective treatments in the future. DOI - https://doi.org/10.18632/oncotarget.28747 Correspondence to - Susan E. Waltz - susan.waltz@uc.edu, and Vinita Takiar - takiarva@ucmail.uc.edu Video short - https://www.youtube.com/watch?v=RD2W-F3_aX4 About Oncotarget: Website - https://www.oncotarget.com Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Why You Should Listen:  In this episode, you will learn about chronic kidney disease and how to address the Kidneydemic with Renology. About My Guest: My guest for this episode is Dr. Robin Rose.  Robin Rose, MD began a journey into holistic healing in her teens in the mid-sixties beginning with nutrition and botanical medicine and yoga and meditation.  Over the years her journey included time living in India and working with both village doctors and healers.  She became a health food chef and inspired many to change their habits.  Before long she was enrolled in an RN program and then a family nurse practitioner program.  Aware that the education wasn't complete, she attended University of Arizona College of Medicine; while also serving as a medical student board member for the American Holistic Medical Association.  During residency, she continued learning Chinese medicine, acupuncture, osteopathy, energy medicine, and herbal medicine.  Her main practice was in Ashland, Oregon where she served a community eager to integrate many healing modalities into the conventional setting, including innovative care in the hospital.  In the past decade after her own alarming health challenges with kidney cancer and advanced kidney disease, she became agile in regenerative medical approaches to kidney care.  She created a new specialty called Renology; a new concept of "Kidney Success" not Kidney Failure.  When she discovered peptides and especially bioregulator peptides, she led the brigade to new heights of seeing success in a field that had not embraced this kind of care.  Her recent book "Renology Peptides" is a nearly 800 page text on how to achieve this renewal of health.  Her current intention is to raise awareness of the role of kidney in wellbeing and how we can all celebrate this success.  Key Takeaways: What is the purpose of the kidneys? What symptoms are observed in chronic kidney disease? Is kidney disease a catabolic process? Is kidney disease genetic or epigenetic? What are the stages of kidney disease? What are the best tests and lab markers? What might elevations or phosphorous or potassium suggest? What is the kidney-gut axis? What is the role of endothelial health in kidney disease? What role do the mitochondria play?  How do infections and environmental toxicants contribute to kidney disease? What is the role of oxalates in kidney health? How might carbon dioxide guide treatment? Does cellular senescence play a role? What is the connection between the kidneys and the teeth? How do the limbic system and mental/emotional health impact the kidneys? What treatment intervention warrant exploration? Where do dialysis and transplantation come into the discussion? What role might peptides and peptide bioregulators play? Connect With My Guest:  RenologyIsKidneySuccess.com Interview Date: May 21, 2025 Transcript: To review a transcript of this show, visit https://BetterHealthGuy.com/Episode217. Additional Information: To learn more, visit https://BetterHealthGuy.com. Follow Me on Social Media: Facebook - https://facebook.com/betterhealthguy Instagram - https://instagram.com/betterhealthguy X - https://twitter.com/betterhealthguy TikTok - https://tiktok.com/@betterhealthguy Disclaimer:  The content of this show is for informational purposes only and is not intended to diagnose, treat, or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority. 

Why You Should Listen:  In this episode, you will learn about chronic kidney disease and how to address the Kidneydemic with Renology. About My Guest: My guest for this episode is Dr. Robin Rose.  Robin Rose, MD began a journey into holistic healing in her teens in the mid-sixties beginning with nutrition and botanical medicine and yoga and meditation.  Over the years her journey included time living in India and working with both village doctors and healers.  She became a health food chef and inspired many to change their habits.  Before long she was enrolled in an RN program and then a family nurse practitioner program.  Aware that the education wasn't complete, she attended University of Arizona College of Medicine; while also serving as a medical student board member for the American Holistic Medical Association.  During residency, she continued learning Chinese medicine, acupuncture, osteopathy, energy medicine, and herbal medicine.  Her main practice was in Ashland, Oregon where she served a community eager to integrate many healing modalities into the conventional setting, including innovative care in the hospital.  In the past decade after her own alarming health challenges with kidney cancer and advanced kidney disease, she became agile in regenerative medical approaches to kidney care.  She created a new specialty called Renology; a new concept of "Kidney Success" not Kidney Failure.  When she discovered peptides and especially bioregulator peptides, she led the brigade to new heights of seeing success in a field that had not embraced this kind of care.  Her recent book "Renology Peptides" is a nearly 800 page text on how to achieve this renewal of health.  Her current intention is to raise awareness of the role of kidney in wellbeing and how we can all celebrate this success.  Key Takeaways: What is the purpose of the kidneys? What symptoms are observed in chronic kidney disease? Is kidney disease a catabolic process? Is kidney disease genetic or epigenetic? What are the stages of kidney disease? What are the best tests and lab markers? What might elevations or phosphorous or potassium suggest? What is the kidney-gut axis? What is the role of endothelial health in kidney disease? What role do the mitochondria play?  How do infections and environmental toxicants contribute to kidney disease? What is the role of oxalates in kidney health? How might carbon dioxide guide treatment? Does cellular senescence play a role? What is the connection between the kidneys and the teeth? How do the limbic system and mental/emotional health impact the kidneys? What treatment intervention warrant exploration? Where do dialysis and transplantation come into the discussion? What role might peptides and peptide bioregulators play? Connect With My Guest:  RenologyIsKidneySuccess.com Interview Date: May 21, 2025 Transcript: To review a transcript of this show, visit https://BetterHealthGuy.com/Episode218. Additional Information: To learn more, visit https://BetterHealthGuy.com. Follow Me on Social Media: Facebook - https://facebook.com/betterhealthguy Instagram - https://instagram.com/betterhealthguy X - https://twitter.com/betterhealthguy TikTok - https://tiktok.com/@betterhealthguy Disclaimer:  The content of this show is for informational purposes only and is not intended to diagnose, treat, or cure any illness or medical condition. Nothing in today's discussion is meant to serve as medical advice or as information to facilitate self-treatment. As always, please discuss any potential health-related decisions with your own personal medical authority.