Podcasts about her2

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

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

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

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

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

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

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

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

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

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

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

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

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

En esta cápsula de ESMO 2025 EXPRESS, el Dr. Sergio Vázquez Estévez, oncólogo médico adscrito al Hospital Universitario Lucus Augusti en Lugo, España, nos habla sobre los principales avances presentados en tumores genitourinarios.El experto comenta lo siguiente:Durante el Congreso Anual de la Sociedad Europea de Oncología Médica 2025, se presentaron resultados que redefinen el manejo de los tumores genitourinarios, destacando avances en cáncer de vejiga, renal y de próstata.En cáncer de vejiga no músculo infiltrante, el estudio POTOMAC (fase III) mostró que durvalumab intravenoso más BCG intravesical mejora la supervivencia libre de enfermedad frente a BCG solo. Sin embargo, se debate si este beneficio justifica la toxicidad de grado 3 (~20%) y si la supervivencia libre de cistectomía debería considerarse el objetivo clínico más relevante.En cáncer de vejiga músculo infiltrante, el ensayo EV-303 fue uno de los más destacados del congreso: la combinación enfortumab vedotin + pembrolizumab en el contexto perioperatorio superó al tratamiento estándar (cistectomía radical más quimioterapia con cisplatino) con mejoras significativas en supervivencia libre de enfermedad, supervivencia global y tasa de respuestas patológicas completas (~57%). Estos resultados abren la posibilidad de estrategias futuras de preservación vesical basadas en ctDNA y resonancia magnética.En el escenario metastásico, un estudio fase III en pacientes con expresión alta de HER2 (1–3 +) demostró que la combinación de un anticuerpo conjugado anti-HER2 (sistema B2C1) con el anti-PD-1 doriplimab mejora la supervivencia libre de enfermedad y global frente al doblete con platino. No obstante, la tasa de respuestas completas (

As pharmaphorum reported during ESMO 2025, fresh from a return to oncology with the FDA approval of zongertinib as a treatment for HER2-positive non-small cell lung cancer (NSCLC), tumour shrinkage observed by investigator review - Boehringer Ingelheim is racing to expand its label. As the company reported new data at the Congress from the phase 1b Beamion LUNG-1 study, underpinning the approval of zongertinib (Hernexeos) as a second-line therapy, web editor Nicole Raleigh spoke with Lykke Hinsch Gylvin, chief medical officer of Boehringer Ingelheim, and Itziar Canamasas, Boehringer's head of oncology, offsite in Berlin. Discussing also Boehringer's novel T-cell engager obrixtamig in combination with standard of care chemoimmunotherapy for patients with extensive-stage small cell lung carcinoma, Gylvin and Canamasas make clear Boehringer's oncology foothold and commitment to making an unprecedented impact on the lives of those affected by cancer through innovative research. Certainly, patient engagement, patient quality of life, and patient trial co-creation are core Boehringer Ingelheim concerns. This and other reportage from ESMO 2025 can be found here. You can listen to episode 211 of the pharmaphorum podcast in the player below, download the episode to your computer, or find it - and subscribe to the rest of the series – on Apple Podcasts, Spotify, Overcast, Pocket Casts, Podbean, and pretty much wherever else you download your other podcasts from.

En esta cápsula de ESMO 2025 EXPRESS, el Dr. Luis Corrales, oncólogo médico adscrito al Centro de Investigación y Manejodel Cáncer en San José, Costa Rica, nos habló sobre los principales avances presentados en oncología torácica. El experto comenta lo siguiente: Durante el Congreso Anual de la Sociedad Europea de Oncología Médica 2025, se dieron a conocer resultados que continúan transformando el tratamiento del cáncer depulmón. Entre ellos destacan los análisis finales del estudio ALEX, que confirman el beneficio sostenido de alectinib frente a crizotinib en pacientes ALK positivos, respaldado por un seguimiento de diez años. Asimismo, se presentaron avances en mutaciones menos frecuentes, como HER2, con nuevas moléculas que demuestran eficacia tanto en líneas avanzadas como en estudios que evalúan su uso en primera línea. También se registraron progresos en el campo de la inmunoterapia, con el desarrollo de agentes novedosos que han mostrado resultados prometedores, especialmente en pacientes que han progresado tras las terapias estándar. Por último, se destacaron los avances observados en el cáncer de pulmón de células pequeñas, una enfermedad históricamente asociada con mal pronóstico, en la que laincorporación de nuevas terapias ha mostrado mejoras significativas en la supervivencia. En conclusión, los resultados presentados en el Congreso Anual de la Sociedad Europea de Oncología Médica 2025 reflejan una evolución constante en la oncología torácicay refuerzan la importancia de ampliar el acceso a estas innovaciones terapéuticas para los pacientes en Latinoamérica.  Fecha de grabación: 19 de octubre de 2025 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 reflejannecesariamente 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 tercerosy 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 EuropeanSociety 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. Gonzalo Giornelli, oncólogo clínico y jefe del Departamento de Gineco-Oncología del Instituto Alexander Fleming en Buenos Aires, Argentina, nos comenta brevemente los avances más relevantes en tumores ginecológicos presentados durante el congreso ESMO 2025.El gran protagonista de este ESMO fue, sin duda, el cáncer de ovario, particularmente en el contexto platino-resistente, una población de mal pronóstico y con necesidad de nuevas alternativas terapéuticas. En este escenario, tres estudios marcaron un antes y un después al demostrar beneficios en sobrevida global.El primero, KEYNOTE-B21, evaluó pembrolizumab más paclitaxel semanal ± bevacizumab frente al estándar de paclitaxel ± bevacizumab. Este estudio mostró una reducción del riesgo de progresión del 28 % y una disminución del riesgo de muerte del 24 %, con un incremento notable en la tasa de respuesta (50 % vs 40 %). El Dr. Giornelli subraya que este régimen se consolida como una nueva opción sin necesidad de selección por PD-L1, aunque advierte que la población estudiada tuvo menor exposición a inhibidores PARP que la práctica actual. Estos resultados llevaron a la aprobación acelerada por la FDA como nuevo estándar en pacientes con cáncer de ovario platino-resistenteEl segundo estudio mencionado fue MIRASOL, con el anticuerpo conjugado mirvetuximab soravtansine, que demostró una reducción del 37 % en el riesgo de progresión y del 32 % en el riesgo de muerte, junto con tasas de respuesta del 42 %. Sin embargo, requiere la sobreexpresión del receptor de folato alfa, presente en alrededor del 36 % de las pacientesEn otras patologías ginecológicas, el Dr. Giornelli resaltó un estudio chino en cáncer de cérvix, que evaluó camrelizumab + famitinib (una combinación similar a pembrolizumab + lenvatinib) frente a quimioterapia sola, mostrando beneficios en PFS, OS y tasa de respuesta, aunque con toxicidades relevantes.Finalmente, en cáncer de endometrio, destacó que se avanza hacia una mayor precisión molecular para definir tratamientos en pacientes sin alteraciones MSI-H o POLE. Además, subrayó la importancia de identificar el subgrupo HER2 positivo, dada la alta tasa de respuesta (> 76 %) observada con trastuzumab deruxtecán en este grupo.El especialista concluye que ESMO 2025 marcó un punto de inflexión en oncología ginecológica, con tres nuevas alternativas terapéuticas para cáncer de ovario platino-resistente y múltiples desarrollos en cáncer de cérvix y endometrio, reafirmando la relevancia de la inmunoterapia y los ADCs como ejes del futuro tratamiento en estos tumores

En esta cápsula de ESMO 2025 EXPRESS, el Dr. Juan Manuel O'Connor, oncólogo médico, jefe de la sección de Tumores Gastrointestinales del Instituto Alexander Fleming en Buenos Aires, Argentina nos comenta brevemente sobre los avances más relevantes sobre tumores gastrointestinales.El experto comenta lo siguiente: Ya se presentaron los datos del estudio MATTERHORN con resultados maduros. Como recordatorio, este estudio marca un nuevo paradigma terapéutico al incorporar la inmunoterapia junto con el esquema FLOT en el entorno perioperatorio del cáncer gástrico o de la unión gastroesofágica. Esto significa que el tratamiento logra aumentar las tasas de curación en pacientes con adenocarcinoma gástrico o de la unión gastroesofágica localmente avanzado.Según el reporte, se observa una reducción cercana al 25% en el riesgo de muerte, y la mediana de supervivencia aún no se ha alcanzado con el seguimiento disponible. Por lo tanto, como mencionaba, este resultado representa un hallazgo relevante que confirma y fortalece los datos presentados previamente en la sesión plenaria de ASCO de este año.De cara al futuro, sería importante considerar análisis por subgrupos, especialmente en pacientes con tumores de tipo difuso o en posibles diferencias relacionadas con el género, dado que se observaron resultados algo inferiores en mujeres. Estos aspectos podrían ser criterios relevantes de estratificación en futuros estudios.En cualquier caso, se trata de un estudio positivo con hallazgos significativos. En esa misma sesión se presentó también el SKYSCRAPER-07, que se enfoca en tumores de tipo escamoso, lo que nos lleva a reflexionar y plantear nuevas preguntas sobre este campo. La pregunta es si existe alguna estrategia adicional para los pacientes que han recibido tratamiento definitivo, y en este contexto se evaluó la combinación de atezolizumab con tiragolumab, un anticuerpo anti-TIGIT, como posible alternativa terapéutica, aunque el estudio no alcanzó su objetivo principal predefinido, sí evidenció ciertas señales de actividad que sugieren un potencial beneficio de la inmunoterapia como tratamiento de consolidación en pacientes con enfermedad irresecable.Y finalmente, en el área de los tumores esofagogástricos, para comentar que me llamó la atención, en el advenimiento estos anticuerpos biespecíficos, un nuevo agente que se presentó justamente en combinación o comparando con el esquema de quimioterapia para pacientes con cáncer gástrico, HER2 positivo.Y para cerrar, en el campo de los tumores esofagogástricos, me pareció interesante destacar el avance de los anticuerpos biespecíficos, con la presentación de un nuevo agente evaluado en comparación con la quimioterapia estándar en pacientes con cáncer gástrico HER2 positivo.Entre otros temas.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.

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

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

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

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

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

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

In this podcast episode, breast cancer experts Manali Bhave, MD, and Erin F. Cobain, MD, discuss their management of patients with HR-positive/HER2-negative metastatic breast cancer including the current treatment algorithm, implementing genomic testing for assessing molecular resistance and guiding treatment decisions, and answering healthcare professional questions on how to personalize therapy for these patients. Supported by an educational grant from Lilly.Faculty:Manali Bhave, MDMedical Director, Phase I Clinical Trials UnitAssistant ProfessorDepartment of Hematology and OncologyWinship Cancer InstituteEmory UniversityAtlanta, GeorgiaErin F. Cobain, MDAssociate Professor of Internal MedicineDivision of Hematology/OncologyBreast Oncology ProgramUniversity of Michigan Rogel Cancer CenterAnn Arbor, Michigan Link to obtain CME/CE credit:https://bit.ly/4nUJO1OLink to Oncology Breast Cancers with additional educational activities:https://bit.ly/4nNGlBY Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

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

In this podcast episode, Amit Mahipal, MD, MPH, and Shubham Pant, MD, discuss new and emerging therapies for the personalized care of patients with HER2-positive gastroesophageal adenocarcinoma (GEA) and biliary tract cancer (BTC), including:Brief overview of BTC and GEAApproved HER2-directed therapies for BTC and GEA and their mechanisms of actionEfficacy and toxicities of the approved agents and optimal management strategiesKey ongoing trials of HER2-directed therapies in BTC and GEAChallenges faced by healthcare professionals in the management of patients with BTC and/or GEA PresentersAmit Mahipal, MD, MPHDirector, Gastrointestinal Medical Oncology ProgramRuth and Donald Goodman Endowed Chair in GI OncologyProfessor of Medicine, Senior Attending PhysicianUniversity Hospitals Siedman Cancer CenterCase Comprehensive Cancer CenterCase Western Reserve UniversityCleveland, OhioShubham Pant, MDProfessorDepartment of Gastrointestinal (GI) Medical OncologyDepartment of Investigational Cancer TherapeuticsDirector of Clinical ResearchAssociate Director for Early Phase Drug DevelopmentSheikh Ahmed Bin Zayed Al Nahyan CenterMD Anderson Cancer CenterHouston, TexasLink to full program:https://bit.ly/3KL2ank Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

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

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

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Although precision medicine has improved outcomes for many patients, certain rare genetic mutations are still poorly understood, particularly in regions with limited access to genomic testing. Such mutations involve the HER2 gene, better known for its role in breast cancer but also implicated in a small subset of lung cancers. HER2 mutations are found in approximately 2–4% of non-small cell lung cancer (NSCLC) cases and create unique challenges. These tumors can vary significantly in how they appear under a microscope and in how they respond to treatment. Adding to the complexity, most diagnostic and treatment guidelines are based on research from high-income countries, which may not reflect the genetic diversity seen in other parts of the world. To help close this knowledge gap, researchers in Northeastern Brazil conducted one of the first detailed investigations into HER2-mutated NSCLC in Latin America. Their study, recently published in Volume 16 of Oncotarget, reveals a complex and often overlooked form of the disease, highlighting the need for broader access to targeted therapies in underserved populations. Full blog - https://www.oncotarget.org/2025/10/08/new-insights-into-her2-mutated-non-small-cell-lung-cancer-in-brazil/ Paper DOI - https://doi.org/10.18632/oncotarget.28737 Correspondence to - Fabio Tavora - stellacpak@outlook.com Abstract video - https://www.youtube.com/watch?v=hr5R9iDBFFI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28737 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, HER2 mutation, NSCLC, lung cancer, targeted therapy, genomic profiling 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

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Understanding-Endocrine-Resistance-in-HR-HER2-mBC/37323/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Comprehensive-Biomarker-Testing-in-mBC-Informs-Clinical-Decision-Making/37332/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/The-Future-of-PI3K-Inhibition-in-HR-HER2-Breast-Cancer/37339/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/PI3K-Pathway-inhibition-in-HR-HER2-mBC-Mechanistic-Insights/37329/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/PI3K-Pathway-Inhibitors-Safety-and-Tolerability-Profiles/37338/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

CME credits: 0.75 Valid until: 07-10-2026 Claim your CME credit at https://reachmd.com/programs/cme/Case-in-Point-Applying-PI3K-Combinations-in-Early-Recurrent-HR-HER2-mBC/37336/ The PI3K-AKT-mTOR pathway is a crucial signaling network dysregulated in many cancers, promoting cell survival, growth, and proliferation, and often implicated in resistance to cancer therapies. Inhibition of this pathway by PI3K inhibitors disrupts a complex network of cellular processes that contribute to breast cancer, markedly reducing cell proliferation, promoting apoptosis, inhibiting angiogenesis, and ultimately preventing tumor formation and progression. In hormone receptor–positive (HR+), activating PIK3CA mutations occur in approximately 35% to 40% of patients and a variable prevalence across BC subtypes. Testing is thus crucial to ensure appropriate treatment selection. The development of PI3K-targeted agents may revolutionize the treatment landscape for HR+, HER2- metastatic breast cancer (mBC, and due to the recent approval of inavolisib, clinicians must be apprised of both the clinical evidence and best practices regarding the use of this agent. This activity has been designed to review the role of the PI3K-AKT-mTOR pathway in breast cancer, the importance of testing when making clinical decisions, and the role of PI3K-targeted therapies in HR+, HER- mBC.

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

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

Solange Peters, MD, PhD - Pioneering Precision: A Real-World Roadmap to Optimal Outcomes in NTRK Fusion-Positive and HER2-Mutant Advanced NSCLC

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XYR865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 24, 2026.Changing the Scenery in ER+, HER2- MBC With New Oral SERDs and Combinations: Foundations, Evidence, and Practicalities In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AQV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 28, 2026.Visual Exploration of the Evolving Role of Novel Oral SERDs, Other ER-Targeting Therapies, and Rational Combinations in ER+, HER2- MBC In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AQV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 28, 2026.Visual Exploration of the Evolving Role of Novel Oral SERDs, Other ER-Targeting Therapies, and Rational Combinations in ER+, HER2- MBC In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XYR865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 24, 2026.Changing the Scenery in ER+, HER2- MBC With New Oral SERDs and Combinations: Foundations, Evidence, and Practicalities In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/XYR865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 24, 2026.Changing the Scenery in ER+, HER2- MBC With New Oral SERDs and Combinations: Foundations, Evidence, and Practicalities In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/AQV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until September 28, 2026.Visual Exploration of the Evolving Role of Novel Oral SERDs, Other ER-Targeting Therapies, and Rational Combinations in ER+, HER2- MBC In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and METAvivor. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure information is available at the beginning of the video presentation.

Dr. Monty Pal and Dr. Matteo Lambertini discuss a compelling global study on the clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers, the association of pre-diagnostic awareness of BRCA status with prognosis, and the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants. TRANSCRIPT Dr. Monty Pal: Well, hello everyone, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor, and vice chair of medical oncology at the City of Hope Comprehensive Cancer Center in Los Angeles. Now, when we think about genetic testing, whether for patients diagnosed with breast cancer or for other family members of them, it seems to be widely underutilized. Today, we're going to be discussing a recently published study in the Journal of Clinical Oncology that reported on the clinical behavior of breast cancer and specifically young BRCA1 and BRCA2 carriers, and the association of pre-diagnostic awareness of BRCA status with prognosis. I thought this was just a fascinating piece, and I honestly couldn't wait to have this conversation. It's a really compelling paper that highlights the importance of identifying healthy people who are at risk of carrying the BRCA1/2 pathogenic variants, and really the need for genetic counseling and testing to inform people about early detection that could lead to a better prognosis. I'm really delighted to welcome the study's lead author, Dr. Matteo Lambertini. He really needs no introduction. He's very well known in the breast cancer world for his amazing contributions to fertility in the context of breast cancer, to pregnancy in the context of breast cancer, and genetic testing. He's an associate professor at the University of Genova, and a breast cancer medical oncologist at the San Martino Polyclinic Hospital in Genova, Italy.  Dr. Lambertini, thank you so much for joining us today. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a great pleasure. Dr. Monty Pal: Oh, thanks. And just FYI, if you're listening in and you want to hear our disclosures, they're all listed at the transcript of this podcast.  So, I poured through this paper [Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status] yesterday, Dr. Lambertini, and first of all, congratulations on this study. This was a huge international multicenter effort, 4,752 patients. How did you pool all these patients with young breast cancer? Dr. Matteo Lambertini: Thanks a lot for the question. Yes, this was an effort made by several centers all over the world. The main idea behind the creation of this network that we have named as BRCA BCY Collaboration, was to get as many data as possible in a sort of niche patient population in the breast cancer field, meaning women diagnosed with breast cancer at the age of 40 years or younger, and all of them being BRCA carriers. We know that around, in the Western world, around 5% of breast cancer cases are being diagnosed under the age of 40 years, and among them around 10-15% are BRCA carriers. So, I would say it's a relatively rare patient population where we did not have a lot of evidence to support our choices in terms of counseling on treatment, prevention, and oncofertility as well. That was the idea behind the creation of this network that includes many centers. Dr. Monty Pal: Yeah. You know, what's so interesting about this is that you sort of draw this line between patients who have BRCA testing at the time of diagnosis and then BRCA testing earlier in their course and then leading to a diagnosis perhaps. And I think that's where really sort of the dichotomy in outcome sits. Can you maybe elaborate on this and tell us about timing of genetic testing in this study and what that meant ultimately in terms of prognosis? Dr. Matteo Lambertini: In this specific analysis from this large network, including almost 5,000 women with breast cancer diagnosed at the age of 40 years or younger and being a BRCA carrier, we looked specifically into the timing of genetic testing because this is a retrospective study and the criteria for inclusion are those that I have just mentioned, so diagnosis at a young age plus carrying germline BRCA pathogenic or likely pathogenic variant. In this analysis, we have looked into the time the patient has got the genetic testing and particular we focused on two populations: those that were diagnosed, knowing already to be a BRCA carrier, and those that got tested after being diagnosed with breast cancer. And the main findings from this analysis have been that knowing to be a BRCA carrier was associated with a lower stage at the time of diagnosis, meaning more T1 tumors, so a tumor less than 2 cm, more node-negative disease, and this translated into less aggressive treatment, so less often axillary dissection, less often use of chemotherapy and anthracycline-based chemotherapy. And even more importantly, we have seen a better overall survival for those patients that were diagnosed already knowing to be BRCA carriers as compared to those tested after breast cancer diagnosis. These results after adjusting for all the confounding, stage, treatment and so on, there was not significant anymore, meaning that it's not the timing of test per se that is probably leading to a better survival, but it is the fact that knowing to be a BRCA carrier would likely translate into having access to all the preventive measures that we have in this setting and this will translate into an overall survival benefit, so in terms of saving more lives in young BRCA carriers. Dr. Monty Pal: I think it's such an important point, and it's one that I think might sound implicit, right, but it needs to be proven, I think, through a study like this. You know, the fact that finding this early, identifying the mutation, doing enhanced screening, and so forth, is really going to lead to superior clinical outcomes. One of the things that I think many people puzzle over, including myself, is what to do? I personally occasionally will see BRCA altered patients in the context of prostate cancer. But that's a very different population of individuals, right? Typically older men. In young females with BRCA mutation, I guess there's a specific set of considerations around reproductive health. You'd already highlighted preventive strategies, but what sorts of things should we be talking about in the clinics once a patient's diagnosed and once perhaps their breast cancer diagnosis is established? Dr. Matteo Lambertini: Yes, exactly. Knowing to be a BRCA carrier has a lot of implications from prevention to treatment to survivorship issues including reproductive counseling. And this is important not only for the patient that has been diagnosed with breast cancer but also for all the family members that will get tested and maybe identify with this sort of genetic alteration before diagnosis of cancer. Why this is important is because we have access to very effective preventive measures, a few examples: MRI screening, which starts at a very young age and normally young women don't have an effective screening strategy outside the BRCA field. Also, primary preventive measures, for example, risk-reducing surgery. These women are known to have a high risk of breast cancer and high risk of ovarian cancer. So the guidelines are suggesting to undergo risk-reducing salpingo-oophorectomy at a young age, so 35 to 40 years in BRCA1 carrier, 40 to 45 years in BRCA2 carrier. And also risk-reducing mastectomy should be discussed because it is a very effective way to prevent the occurrence of breast cancer. And in some situations, including the setting that we are talking about, so young women with breast cancer, BRCA carrier, also risk-reducing mastectomy has shown to improve overall survival.  On the other side, once diagnosed with breast cancer, nowadays knowing to be or not a BRCA carrier can make a difference in terms of treatment. We have PARP inhibitors in the early setting, in the adjuvant setting as well as in the metastatic setting. And in terms of survivorship implication, one of the critical aspects for young women is the oncofertility care which is even more complicated when we talk about BRCA carriers that are women candidates for gynecological surgery at a very young age. So this sort of counseling is even more complicated. Dr. Monty Pal: One of the other things, and this is subtle in your paper and I hope you don't mind me bringing it up, is the difference between BRCA1 and BRCA2. It really got me thinking about that because there are differences in phenotype and manifestation. Do you mind just expanding on that a little bit for the audience because I think that's a really important reminder that you brought up in the discussion? Dr. Matteo Lambertini: The difference between BRCA1 and BRCA2 carriers has been known that there are different phenotypes of breast cancer that are more often diagnosed in these two different populations. Normally BRCA1 carriers have a higher likelihood to develop a triple negative breast cancer as compared to BRCA2 carriers, more likely to develop a hormone receptor-positive HER2-negative disease. In this study, again, a specific population of young women with breast cancer, we have seen the same findings, mostly triple negative disease in BRCA1 carrier, mostly luminal-like disease in BRCA2 carrier. But what's novel or interesting from this study is to look also at the age at the time of diagnosis of this disease. And particularly in BRCA1 carriers, we should be sort of more careful about diagnosis of breast cancer and also other primary tumors including ovarian cancer because the risk of developing these malignancies is higher even at a younger age as compared to BRCA2 carriers. And this has implications also in the primary and secondary prevention that we were talking about earlier. Dr. Monty Pal: Oh, interesting. I guess the fundamental question then from your paper becomes, how do we get at the right patients for screening for BRCA1 and BRCA2? And I realize our audience here is largely oncologists who are going to be listening to this podcast, oncology providers, MDs, nurses, etc. But maybe speak for a moment to the general practitioner. Are there things that, for instance, a general practitioner should be looking for to say, “Wait a minute, this patient's high risk, we should consider BRCA1, BRCA2 testing or germline screening”? Dr. Matteo Lambertini: Yes, it's a very important question for the breast cancer community. After the updated ASCO guideline, the counseling is way easier because right now the age cutoff goes up to 65 years, meaning that all the patients diagnosed with breast cancer below the age of 65 years should be tested these days. And then above the age of 65, there are different criteria like triple-negative disease or family history. From a general practitioner standpoint, it's of course a bit more difficult, but knowing particularly the family history of the person that they have in front will be crucial to know if there are cases of breast cancer diagnosed at a young age, maybe triple-negative cases, knowing cases of ovarian cancer in first-degree relatives or pancreatic cancer in first-degree relatives, and of course cases of prostate cancer as well. So, I would say probably mostly the family side will be important from a general practitioner perspective.  From an oncology one, the other point that I think is important to stress also based on the data that we have shown in this publication is that having a case of breast cancer known to carry a BRCA pathogenic or likely pathogenic variant. It means that all the people around this case should get tested and if found to be BRCA carrier and healthy carrier, these people should also undergo the primary and secondary prevention strategies because this is very critical also to improve their outcomes and try to avoid the developing of breast or ovarian cancer, but also in the case of diagnosis of this disease, a diagnosis at an earlier stage, as we have seen in this paper. Dr. Monty Pal: Brilliant. I'm going to diverge from our list of questions here and close by asking a question that I have at the top of my mind. You're very young. I know our podcast listeners can't see you, but you're very, very young. Dr. Matteo Lambertini: Thank you. Thank you for that. Not so young but yeah. Dr. Monty Pal: You have nearly 300 papers. Your H-index is 67. You've already made these seminal contributions, as I outlined it from the outset, regarding fertility, regarding use of GnRH analogs, regarding pregnancy and breast cancer. What are you studying now? What are you really excited about right now that you're doing that you think might potentially be practice changing? Give us a little teaser. Dr. Matteo Lambertini: Yeah. Thanks a lot, Dr. Pal. Receiving this compliment from you is fantastic. So, thanks a lot for that. From my side, in terms of my research, I've been interested in the field of breast cancer in young women since the start of my training. I've had very good mentors from Italy, from Europe, from the U.S. I'm still interested in this field, so I think we still have a lot to learn to try to improve the care of young women with breast cancer. For example, the oncofertility care, which is something I worked a lot over the past years. Now with all the new treatment options, there's a sort of new chapter of oncofertility counseling. So, what's the impact of immunotherapy? What's the impact of the new targeted agents?  More on the genetic aspects, now we know that there's not only BRCA1 or BRCA2. There are a lot of other different genes that may increase the risk of breast cancer and other malignancies. And also for these genes, we really don't have a lot of evidence to counsel women on prognosis, treatment, prevention strategy. So we need to learn way more for this special patient population that are quite rare, and so we really need a multicenter academic effort to try to give some evidence in this field. Dr. Monty Pal: Yeah. It's tough because these are rare circumstances, but, you know, I think that you've done really well to sort of define some collective experiences that I think really define therapy. I mean, I just remember when I was in training 25 years ago, just reading through textbooks where all the experience around breast cancer and pregnancy was really just very sort of anecdotal almost, you know? And so it's great to see that the state of the science has moved forward.  Well, gosh, I really enjoyed our conversation today. I think your study really reminds us how powerful genetic information is in terms of improving outcomes. And, you know, hopefully this will lead some individuals to perhaps test more broadly in appropriate settings. So, thank you so much, Matteo, for joining us today with your fantastic insights on the ASCO Daily News Podcast. Dr. Matteo Lambertini: Thank you very much, Dr. Pal. It's a real pleasure. Dr. Monty Pal: And thanks to our listeners too. You'll find a link to Dr. Lambertini's study in the transcript of this episode. Finally, if you value the insights that you heard today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Thanks a ton. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:    Dr. Sumanta (Monty) Pal  @montypal  Dr. Matteo Lambertini @matteolambe   Follow ASCO on social media:     @ASCO on Twitter    ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Monty Pal:   Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview  Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical  Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis  Dr. Matteo Lambertini: Consulting or Advisory Role: Roche, Novartis, Lilly, AstraZeneca, Pfizer, MSD, Exact Sciences, Gilead Sciences, Seagen, Menarini, Nordic Pharma Speakers' Bureau: Takeda, Roche, Lilly, Novartis, Pfizer, Sandoz, Ipsen, Knight Therapeutics, Libbs, Daiichi Sankyo, Gilead Sciences, AstraZeneca, Menarini, AstraZeneca, Menarini Research Funding (Inst.): Gilead Sciences Travel, Accommodations, Expenses: Gilead Sciences, Daiichi Sankyo Europe GmbH, Roche

Featuring an interview with Dr Kevin Kalinsky, including the following topics: Patient-Reported Outcomes from the TROPION-Breast01 Study (0:00) Pernas S et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer (BC): Patient-reported outcomes from the TROPION-Breast01 study. ASCO 2024;Abstract 1006. Indirect Comparison of Sacituzumab Govitecan and Datopotamab Deruxtecan for Advanced Breast Cancer (5:04) Pathak N et al. Indirect comparison of sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) in advanced breast cancer (aBC): Safety and efficacy analysis. San Antonio Breast Cancer Symposium 2024;Abstract P1-02-02. BEGONIA: A Phase Ib/II Study of Datopotamab Deruxtecan with Durvalumab as First-Line Treatment for Unresectable Advanced Triple-Negative Breast Cancer (9:53) Schmid P et al. Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Updated results from BEGONIA, a phase Ib/II study. ESMO 2023;Abstract 379MO. Advances in the Use of TROP2-Targeted Antibody-Drug Conjugates for Breast Cancer: Mechanisms, Clinical Applications and Future Directions (15:35) Tong Y et al. Advances in Trop-2 targeted antibody-drug conjugates for breast cancer: Mechanisms, clinical applications, and future directions. Front Immunol 2024;15:1495675. Abstract CME information and select publications

Featuring an interview with Prof Peter Schmid, including the following topics: Response to immunotherapy in breast cancer subtypes (0:00) Tolerability of TROP2 antibody-drug conjugates (ADCs) for metastatic breast cancer (mBC) (3:51) Approaches to therapy for patients with HR-negative HER2-low and HER2-ultralow mBC (13:03) ADC structure and treatment-related adverse events (19:02) Available data from the Phase III ASCENT-04 trial evaluating sacituzumab govitecan with pembrolizumab as first-line therapy for patients with PD-L1-positive advanced triple-negative breast cancer (23:06) Novel ADCs and bispecific antibodies under investigation for mBC (28:30) Comparing datopotamab deruxtecan and sacituzumab govitecan for HR-positive disease (33:01) Clinical investigator perspectives on the Phase III DESTINY-Breast09 trial evaluating first-line trastuzumab deruxtecan with or without pertuzumab versus THP (docetaxel/rastuzumab/pertuzumab) for HER2-positive mBC (35:06) CME information and select publications

Featuring a slide presentation and related discussion from Prof Peter Schmid, including the following topics: Evolution of the therapeutic landscape for metastatic triple-negative breast cancer; age of immunotherapy (0:00) Case: A woman in her early 40s with no actionable mutations (7:29) Evolution of antibody-drug conjugates (ADCs) in the management of metastatic breast cancer (11:13) TROP2-directed ADCs (15:22) Case: A woman in her early 50s with PD-L1-negative, HR-negative, HER2-low de novo metastatic breast cancer (20:21) Novel strategies utilizing approved and investigational ADCs (23:28) Case: A woman in her early 60s with loss of HER2 expression on disease progression (31:39) ADCs in combination with immunotherapy (32:51) CME information and select publications